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ResearchIn-Press PreviewImmunologyInfectious disease
Open Access | 10.1172/JCI158630
1Department of Molecular Microbiology, Washington University, St. Louis, St. Louis, United States of America
2Washington University in St Louis, The McDonnell Genome Institute, St. Louis, United States of America
3Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United States of America
4Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United Kingdom
5Department of Medicine, University of Rochester Medical Center, Rochester, United States of America
6South African Tuberculosis Vaccine Initiative, University of Cape Town, Cape Town, South Africa
7Biotechnology and Cell Signalling, CNRS/ UMR 7242, Illkirch, France
8Department of Molecular Microbiology, The University of Chicago, Chicago, United States of America
9Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
10Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, United States of America
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1Department of Molecular Microbiology, Washington University, St. Louis, St. Louis, United States of America
2Washington University in St Louis, The McDonnell Genome Institute, St. Louis, United States of America
3Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United States of America
4Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United Kingdom
5Department of Medicine, University of Rochester Medical Center, Rochester, United States of America
6South African Tuberculosis Vaccine Initiative, University of Cape Town, Cape Town, South Africa
7Biotechnology and Cell Signalling, CNRS/ UMR 7242, Illkirch, France
8Department of Molecular Microbiology, The University of Chicago, Chicago, United States of America
9Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
10Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, United States of America
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1Department of Molecular Microbiology, Washington University, St. Louis, St. Louis, United States of America
2Washington University in St Louis, The McDonnell Genome Institute, St. Louis, United States of America
3Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United States of America
4Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United Kingdom
5Department of Medicine, University of Rochester Medical Center, Rochester, United States of America
6South African Tuberculosis Vaccine Initiative, University of Cape Town, Cape Town, South Africa
7Biotechnology and Cell Signalling, CNRS/ UMR 7242, Illkirch, France
8Department of Molecular Microbiology, The University of Chicago, Chicago, United States of America
9Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
10Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, United States of America
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Rosa, B.
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1Department of Molecular Microbiology, Washington University, St. Louis, St. Louis, United States of America
2Washington University in St Louis, The McDonnell Genome Institute, St. Louis, United States of America
3Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United States of America
4Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United Kingdom
5Department of Medicine, University of Rochester Medical Center, Rochester, United States of America
6South African Tuberculosis Vaccine Initiative, University of Cape Town, Cape Town, South Africa
7Biotechnology and Cell Signalling, CNRS/ UMR 7242, Illkirch, France
8Department of Molecular Microbiology, The University of Chicago, Chicago, United States of America
9Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
10Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, United States of America
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1Department of Molecular Microbiology, Washington University, St. Louis, St. Louis, United States of America
2Washington University in St Louis, The McDonnell Genome Institute, St. Louis, United States of America
3Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United States of America
4Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United Kingdom
5Department of Medicine, University of Rochester Medical Center, Rochester, United States of America
6South African Tuberculosis Vaccine Initiative, University of Cape Town, Cape Town, South Africa
7Biotechnology and Cell Signalling, CNRS/ UMR 7242, Illkirch, France
8Department of Molecular Microbiology, The University of Chicago, Chicago, United States of America
9Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
10Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, United States of America
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Cho, S.
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1Department of Molecular Microbiology, Washington University, St. Louis, St. Louis, United States of America
2Washington University in St Louis, The McDonnell Genome Institute, St. Louis, United States of America
3Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United States of America
4Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United Kingdom
5Department of Medicine, University of Rochester Medical Center, Rochester, United States of America
6South African Tuberculosis Vaccine Initiative, University of Cape Town, Cape Town, South Africa
7Biotechnology and Cell Signalling, CNRS/ UMR 7242, Illkirch, France
8Department of Molecular Microbiology, The University of Chicago, Chicago, United States of America
9Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
10Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, United States of America
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1Department of Molecular Microbiology, Washington University, St. Louis, St. Louis, United States of America
2Washington University in St Louis, The McDonnell Genome Institute, St. Louis, United States of America
3Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United States of America
4Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United Kingdom
5Department of Medicine, University of Rochester Medical Center, Rochester, United States of America
6South African Tuberculosis Vaccine Initiative, University of Cape Town, Cape Town, South Africa
7Biotechnology and Cell Signalling, CNRS/ UMR 7242, Illkirch, France
8Department of Molecular Microbiology, The University of Chicago, Chicago, United States of America
9Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
10Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, United States of America
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1Department of Molecular Microbiology, Washington University, St. Louis, St. Louis, United States of America
2Washington University in St Louis, The McDonnell Genome Institute, St. Louis, United States of America
3Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United States of America
4Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United Kingdom
5Department of Medicine, University of Rochester Medical Center, Rochester, United States of America
6South African Tuberculosis Vaccine Initiative, University of Cape Town, Cape Town, South Africa
7Biotechnology and Cell Signalling, CNRS/ UMR 7242, Illkirch, France
8Department of Molecular Microbiology, The University of Chicago, Chicago, United States of America
9Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
10Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, United States of America
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Schreiber, V.
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1Department of Molecular Microbiology, Washington University, St. Louis, St. Louis, United States of America
2Washington University in St Louis, The McDonnell Genome Institute, St. Louis, United States of America
3Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United States of America
4Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United Kingdom
5Department of Medicine, University of Rochester Medical Center, Rochester, United States of America
6South African Tuberculosis Vaccine Initiative, University of Cape Town, Cape Town, South Africa
7Biotechnology and Cell Signalling, CNRS/ UMR 7242, Illkirch, France
8Department of Molecular Microbiology, The University of Chicago, Chicago, United States of America
9Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
10Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, United States of America
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1Department of Molecular Microbiology, Washington University, St. Louis, St. Louis, United States of America
2Washington University in St Louis, The McDonnell Genome Institute, St. Louis, United States of America
3Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United States of America
4Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United Kingdom
5Department of Medicine, University of Rochester Medical Center, Rochester, United States of America
6South African Tuberculosis Vaccine Initiative, University of Cape Town, Cape Town, South Africa
7Biotechnology and Cell Signalling, CNRS/ UMR 7242, Illkirch, France
8Department of Molecular Microbiology, The University of Chicago, Chicago, United States of America
9Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
10Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, United States of America
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1Department of Molecular Microbiology, Washington University, St. Louis, St. Louis, United States of America
2Washington University in St Louis, The McDonnell Genome Institute, St. Louis, United States of America
3Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United States of America
4Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United Kingdom
5Department of Medicine, University of Rochester Medical Center, Rochester, United States of America
6South African Tuberculosis Vaccine Initiative, University of Cape Town, Cape Town, South Africa
7Biotechnology and Cell Signalling, CNRS/ UMR 7242, Illkirch, France
8Department of Molecular Microbiology, The University of Chicago, Chicago, United States of America
9Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
10Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, United States of America
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1Department of Molecular Microbiology, Washington University, St. Louis, St. Louis, United States of America
2Washington University in St Louis, The McDonnell Genome Institute, St. Louis, United States of America
3Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United States of America
4Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United Kingdom
5Department of Medicine, University of Rochester Medical Center, Rochester, United States of America
6South African Tuberculosis Vaccine Initiative, University of Cape Town, Cape Town, South Africa
7Biotechnology and Cell Signalling, CNRS/ UMR 7242, Illkirch, France
8Department of Molecular Microbiology, The University of Chicago, Chicago, United States of America
9Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
10Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, United States of America
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Kaushal, D.
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1Department of Molecular Microbiology, Washington University, St. Louis, St. Louis, United States of America
2Washington University in St Louis, The McDonnell Genome Institute, St. Louis, United States of America
3Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United States of America
4Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United Kingdom
5Department of Medicine, University of Rochester Medical Center, Rochester, United States of America
6South African Tuberculosis Vaccine Initiative, University of Cape Town, Cape Town, South Africa
7Biotechnology and Cell Signalling, CNRS/ UMR 7242, Illkirch, France
8Department of Molecular Microbiology, The University of Chicago, Chicago, United States of America
9Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
10Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, United States of America
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Scriba, T.
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1Department of Molecular Microbiology, Washington University, St. Louis, St. Louis, United States of America
2Washington University in St Louis, The McDonnell Genome Institute, St. Louis, United States of America
3Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United States of America
4Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United Kingdom
5Department of Medicine, University of Rochester Medical Center, Rochester, United States of America
6South African Tuberculosis Vaccine Initiative, University of Cape Town, Cape Town, South Africa
7Biotechnology and Cell Signalling, CNRS/ UMR 7242, Illkirch, France
8Department of Molecular Microbiology, The University of Chicago, Chicago, United States of America
9Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
10Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, United States of America
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Khader, S.
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Published May 18, 2023 - More info
The ADP ribosyl transferases (PARPs 1–17) regulate diverse cellular processes, including DNA damage repair. PARPs are classified based on their ability to catalyze poly-ADP-ribosylation (PARylation) or mono-ADP-ribosylation (MARylation). While PARP9 mRNA expression is significantly increased in progressive human tuberculosis (TB), its participation in host immunity to TB is unknown. Here, we show that PARP9 mRNA encoding the MARylating PARP9 enzyme is upregulated during TB in humans and mice and provide evidence of a critical modulatory role for PARP9 in DNA damage, cGAS and type I IFN production during TB. Thus, Parp9-deficient mice are susceptible to Mtb infection and exhibit increased TB disease, cGAS expression, cGAMP and type I IFN production along with upregulation of complement and coagulation pathways. Enhanced Mtb susceptibility is type I IFN-dependent, as blockade of IFNAR signaling reversed the enhanced susceptibility of Parp9-/- mice. Thus, in sharp contrast with PARP9 enhancement of type I IFN production in viral infections, this member of the MAR family plays a protective role by limiting type I IFN responses during TB.