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ResearchIn-Press PreviewCOVID-19Inflammation Open Access | 10.1172/JCI163105

C5aR1 signaling triggers lung immunopathology in COVID-19 through neutrophil extracellular traps

Bruna M.S. Silva,1 Giovanni F. Gomes,2 Flavio P. Veras,3 Seppe Cambier,4 Gabriel V.L. Silva,1 Andreza U. Quadros,2 Diego B. Caetité,2 Daniele C. Nascimento,2 Camila M.S. Silva,1 Juliana C. Costa Silva,2 Samara Damasceno,2 Ayda H. Schneider,2 Fabio Beretta,4 Sabrina S. Batah,5 Icaro M.S. Castro,6 Isadora M. Paiva,2 Tamara Rodrigues,1 Ana Salina,1 Ronaldo Martins,7 Guilherme C. Martelossi Cebinelli,8 Naira L. Bibo,2 Daniel Macedo de Melo Jorge,7 Helder I. Nakaya,9 Dario S. Zamboni,10 Luiz O. Leiria,2 Alexandre T. Fabro,5 José C. Alves-Filho,2 Eurico Arruda,7 Paulo Louzada-Junior,11 Renê D.R. Oliveira,11 Larissa D. Cunha,10 Pierre Van Mol,12 Lore Vanderbeke,4 Simon Feys,4 Els Wauters,12 Laura Brandolini,13 Andrea Aramini,13 Fernando Q. Cunha,2 Jörg Köhl,14 Marcello Allegretti,13 Diether Lambrechts,16 Joost Wauters,4 Paul Proost,4 and Thiago M. Cunha2

1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

Find articles by Silva, B. in: JCI | PubMed | Google Scholar

1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

Find articles by Gomes, G. in: JCI | PubMed | Google Scholar |

1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

Find articles by Veras, F. in: JCI | PubMed | Google Scholar |

1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

Find articles by Cambier, S. in: JCI | PubMed | Google Scholar |

1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

Find articles by Silva, G. in: JCI | PubMed | Google Scholar

1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

Find articles by Quadros, A. in: JCI | PubMed | Google Scholar

1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

Find articles by Caetité, D. in: JCI | PubMed | Google Scholar |

1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

Find articles by Nascimento, D. in: JCI | PubMed | Google Scholar |

1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

Find articles by Silva, C. in: JCI | PubMed | Google Scholar |

1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

Find articles by Costa Silva, J. in: JCI | PubMed | Google Scholar |

1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

Find articles by Damasceno, S. in: JCI | PubMed | Google Scholar |

1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

Find articles by Schneider, A. in: JCI | PubMed | Google Scholar

1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

Find articles by Beretta, F. in: JCI | PubMed | Google Scholar |

1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

Find articles by Batah, S. in: JCI | PubMed | Google Scholar |

1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

Find articles by Castro, I. in: JCI | PubMed | Google Scholar |

1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

Find articles by Paiva, I. in: JCI | PubMed | Google Scholar |

1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

Find articles by Louzada-Junior, P. in: JCI | PubMed | Google Scholar |

1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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1Immunology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

2Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

3Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

4Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

5Department of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

6Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil

7Virology Research Center and Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

8Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Ribeirão Preto, Brazil

9Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Sao Paulo, Brazil

10Department of Cell and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

11Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo , Ribeirão Preto, Brazil

12Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

13Research and Early Development, Dompe Farmaceutici SpA, L'Aquila, Italy

14Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany

15Research and Early Development, Dompe Farmaceutici SpA, Aquila, Italy

16Department of Human Genetics, VIB-KU Leuven, Leuven, Belgium

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Published April 27, 2023 - More info

J Clin Invest. https://doi.org/10.1172/JCI163105.
Copyright © 2023, Silva et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published April 27, 2023 - Version history
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Abstract

Patients with severe COVID-19 develop acute respiratory distress syndrome (ARDS) that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that complement component 5a (C5a), through its cellular receptor C5aR1, has potent proinflammatory actions, and plays immunopathological roles in inflammatory diseases, we investigated whether C5a/C5aR1 pathway could be involved in COVID-19 pathophysiology. C5a/C5aR1 signaling increased locally in the lung, especially in neutrophils of critically ill COVID-19 patients compared to patients with influenza infection, as well as in the lung tissue of K18-hACE2 Tg mice (Tg mice) infected with SARS-CoV-2. Genetic and pharmacological inhibition of C5aR1 signaling ameliorated lung immunopathology in Tg-infected mice. Mechanistically, we found that C5aR1 signaling drives neutrophil extracellular trap (NET)s-dependent immunopathology. These data confirm the immunopathological role of C5a/C5aR1 signaling in COVID-19 and indicate that antagonists of C5aR1 could be useful for COVID-19 treatment.

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