Review 10.1172/JCI128877

Targeting innate immunity for tuberculosis vaccination

Shabaana A. Khader,1 Maziar Divangahi,2 Willem Hanekom,3 Philip C. Hill,4 Markus Maeurer,5,6 Karen W. Makar,3 Katrin D. Mayer-Barber,7 Musa M. Mhlanga,8 Elisa Nemes,9 Larry S. Schlesinger,10 Reinout van Crevel,11 Raman (Krishna) Vankayalapati,12 Ramnik J. Xavier,13,14,15,16 Mihai G. Netea,11,17 and on behalf of the Bill and Melinda Gates Foundation Collaboration for TB Vaccine Discovery Innate Immunity Working Group1818

1Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.

2Meakins-Christie Laboratories, Department of Medicine, Department of Microbiology and Immunology, and Department of Pathology, McGill International TB Centre, McGill University Health Centre, Montreal, Quebec, Canada.

3Bill & Melinda Gates Foundation, Seattle, Washington, USA.

4Centre for International Health, Department of Preventive and Social Medicine, University of Otago Medical School, Dunedin, New Zealand.

5Department of Oncology/Haematology, Krankenhaus Nordwest (KHNW), Frankfurt, Germany,

6ImmunoSurgery Unit, Champalimaud Foundation, Lisbon, Portugal.

7Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.

8Division of Chemical Systems & Synthetic Biology, Institute for Infectious Disease & Molecular Medicine (IDM), Faculty of Health Sciences, Department of Integrative Biomedical Sciences, and

9South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.

10Texas Biomedical Research Institute, San Antonio, Texas, USA.

11Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.

12Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.

13Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

14Center for Computational and Integrative Biology and

15Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

16Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

17Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.

18The Working Group is detailed in Supplemental Acknowledgments.

Address correspondence to: Shabaana A. Khader, Department of Molecular Microbiology, Washington University in St.Louis, Campus Box 8230, 660 South Euclid Avenue, St.Louis Missouri 63110-1093, USA. Phone: 314.286.1590; Email: khader@wustl.edu. Or to: Mihai G. Netea, Department of Internal Medicine, Radboud University, Medical Center, PO Box 9101, 6500HB, Nijmegen, Netherlands. Phone: 31.0.24.361.46.52; Email:mihai.netea@radboudumc.nl.

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1Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.

2Meakins-Christie Laboratories, Department of Medicine, Department of Microbiology and Immunology, and Department of Pathology, McGill International TB Centre, McGill University Health Centre, Montreal, Quebec, Canada.

3Bill & Melinda Gates Foundation, Seattle, Washington, USA.

4Centre for International Health, Department of Preventive and Social Medicine, University of Otago Medical School, Dunedin, New Zealand.

5Department of Oncology/Haematology, Krankenhaus Nordwest (KHNW), Frankfurt, Germany,

6ImmunoSurgery Unit, Champalimaud Foundation, Lisbon, Portugal.

7Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.

8Division of Chemical Systems & Synthetic Biology, Institute for Infectious Disease & Molecular Medicine (IDM), Faculty of Health Sciences, Department of Integrative Biomedical Sciences, and

9South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.

10Texas Biomedical Research Institute, San Antonio, Texas, USA.

11Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.

12Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.

13Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

14Center for Computational and Integrative Biology and

15Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

16Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

17Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.

18The Working Group is detailed in Supplemental Acknowledgments.

Address correspondence to: Shabaana A. Khader, Department of Molecular Microbiology, Washington University in St.Louis, Campus Box 8230, 660 South Euclid Avenue, St.Louis Missouri 63110-1093, USA. Phone: 314.286.1590; Email: khader@wustl.edu. Or to: Mihai G. Netea, Department of Internal Medicine, Radboud University, Medical Center, PO Box 9101, 6500HB, Nijmegen, Netherlands. Phone: 31.0.24.361.46.52; Email:mihai.netea@radboudumc.nl.

Find articles by Divangahi, M. in: JCI | PubMed | Google Scholar

1Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.

2Meakins-Christie Laboratories, Department of Medicine, Department of Microbiology and Immunology, and Department of Pathology, McGill International TB Centre, McGill University Health Centre, Montreal, Quebec, Canada.

3Bill & Melinda Gates Foundation, Seattle, Washington, USA.

4Centre for International Health, Department of Preventive and Social Medicine, University of Otago Medical School, Dunedin, New Zealand.

5Department of Oncology/Haematology, Krankenhaus Nordwest (KHNW), Frankfurt, Germany,

6ImmunoSurgery Unit, Champalimaud Foundation, Lisbon, Portugal.

7Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.

8Division of Chemical Systems & Synthetic Biology, Institute for Infectious Disease & Molecular Medicine (IDM), Faculty of Health Sciences, Department of Integrative Biomedical Sciences, and

9South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.

10Texas Biomedical Research Institute, San Antonio, Texas, USA.

11Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.

12Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.

13Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

14Center for Computational and Integrative Biology and

15Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

16Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

17Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.

18The Working Group is detailed in Supplemental Acknowledgments.

Address correspondence to: Shabaana A. Khader, Department of Molecular Microbiology, Washington University in St.Louis, Campus Box 8230, 660 South Euclid Avenue, St.Louis Missouri 63110-1093, USA. Phone: 314.286.1590; Email: khader@wustl.edu. Or to: Mihai G. Netea, Department of Internal Medicine, Radboud University, Medical Center, PO Box 9101, 6500HB, Nijmegen, Netherlands. Phone: 31.0.24.361.46.52; Email:mihai.netea@radboudumc.nl.

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1Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.

2Meakins-Christie Laboratories, Department of Medicine, Department of Microbiology and Immunology, and Department of Pathology, McGill International TB Centre, McGill University Health Centre, Montreal, Quebec, Canada.

3Bill & Melinda Gates Foundation, Seattle, Washington, USA.

4Centre for International Health, Department of Preventive and Social Medicine, University of Otago Medical School, Dunedin, New Zealand.

5Department of Oncology/Haematology, Krankenhaus Nordwest (KHNW), Frankfurt, Germany,

6ImmunoSurgery Unit, Champalimaud Foundation, Lisbon, Portugal.

7Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.

8Division of Chemical Systems & Synthetic Biology, Institute for Infectious Disease & Molecular Medicine (IDM), Faculty of Health Sciences, Department of Integrative Biomedical Sciences, and

9South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.

10Texas Biomedical Research Institute, San Antonio, Texas, USA.

11Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.

12Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.

13Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

14Center for Computational and Integrative Biology and

15Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

16Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

17Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.

18The Working Group is detailed in Supplemental Acknowledgments.

Address correspondence to: Shabaana A. Khader, Department of Molecular Microbiology, Washington University in St.Louis, Campus Box 8230, 660 South Euclid Avenue, St.Louis Missouri 63110-1093, USA. Phone: 314.286.1590; Email: khader@wustl.edu. Or to: Mihai G. Netea, Department of Internal Medicine, Radboud University, Medical Center, PO Box 9101, 6500HB, Nijmegen, Netherlands. Phone: 31.0.24.361.46.52; Email:mihai.netea@radboudumc.nl.

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1Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.

2Meakins-Christie Laboratories, Department of Medicine, Department of Microbiology and Immunology, and Department of Pathology, McGill International TB Centre, McGill University Health Centre, Montreal, Quebec, Canada.

3Bill & Melinda Gates Foundation, Seattle, Washington, USA.

4Centre for International Health, Department of Preventive and Social Medicine, University of Otago Medical School, Dunedin, New Zealand.

5Department of Oncology/Haematology, Krankenhaus Nordwest (KHNW), Frankfurt, Germany,

6ImmunoSurgery Unit, Champalimaud Foundation, Lisbon, Portugal.

7Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.

8Division of Chemical Systems & Synthetic Biology, Institute for Infectious Disease & Molecular Medicine (IDM), Faculty of Health Sciences, Department of Integrative Biomedical Sciences, and

9South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.

10Texas Biomedical Research Institute, San Antonio, Texas, USA.

11Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.

12Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.

13Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

14Center for Computational and Integrative Biology and

15Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

16Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

17Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.

18The Working Group is detailed in Supplemental Acknowledgments.

Address correspondence to: Shabaana A. Khader, Department of Molecular Microbiology, Washington University in St.Louis, Campus Box 8230, 660 South Euclid Avenue, St.Louis Missouri 63110-1093, USA. Phone: 314.286.1590; Email: khader@wustl.edu. Or to: Mihai G. Netea, Department of Internal Medicine, Radboud University, Medical Center, PO Box 9101, 6500HB, Nijmegen, Netherlands. Phone: 31.0.24.361.46.52; Email:mihai.netea@radboudumc.nl.

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1Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.

2Meakins-Christie Laboratories, Department of Medicine, Department of Microbiology and Immunology, and Department of Pathology, McGill International TB Centre, McGill University Health Centre, Montreal, Quebec, Canada.

3Bill & Melinda Gates Foundation, Seattle, Washington, USA.

4Centre for International Health, Department of Preventive and Social Medicine, University of Otago Medical School, Dunedin, New Zealand.

5Department of Oncology/Haematology, Krankenhaus Nordwest (KHNW), Frankfurt, Germany,

6ImmunoSurgery Unit, Champalimaud Foundation, Lisbon, Portugal.

7Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.

8Division of Chemical Systems & Synthetic Biology, Institute for Infectious Disease & Molecular Medicine (IDM), Faculty of Health Sciences, Department of Integrative Biomedical Sciences, and

9South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.

10Texas Biomedical Research Institute, San Antonio, Texas, USA.

11Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.

12Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.

13Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

14Center for Computational and Integrative Biology and

15Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

16Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

17Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.

18The Working Group is detailed in Supplemental Acknowledgments.

Address correspondence to: Shabaana A. Khader, Department of Molecular Microbiology, Washington University in St.Louis, Campus Box 8230, 660 South Euclid Avenue, St.Louis Missouri 63110-1093, USA. Phone: 314.286.1590; Email: khader@wustl.edu. Or to: Mihai G. Netea, Department of Internal Medicine, Radboud University, Medical Center, PO Box 9101, 6500HB, Nijmegen, Netherlands. Phone: 31.0.24.361.46.52; Email:mihai.netea@radboudumc.nl.

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1Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.

2Meakins-Christie Laboratories, Department of Medicine, Department of Microbiology and Immunology, and Department of Pathology, McGill International TB Centre, McGill University Health Centre, Montreal, Quebec, Canada.

3Bill & Melinda Gates Foundation, Seattle, Washington, USA.

4Centre for International Health, Department of Preventive and Social Medicine, University of Otago Medical School, Dunedin, New Zealand.

5Department of Oncology/Haematology, Krankenhaus Nordwest (KHNW), Frankfurt, Germany,

6ImmunoSurgery Unit, Champalimaud Foundation, Lisbon, Portugal.

7Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.

8Division of Chemical Systems & Synthetic Biology, Institute for Infectious Disease & Molecular Medicine (IDM), Faculty of Health Sciences, Department of Integrative Biomedical Sciences, and

9South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.

10Texas Biomedical Research Institute, San Antonio, Texas, USA.

11Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.

12Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.

13Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

14Center for Computational and Integrative Biology and

15Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

16Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

17Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.

18The Working Group is detailed in Supplemental Acknowledgments.

Address correspondence to: Shabaana A. Khader, Department of Molecular Microbiology, Washington University in St.Louis, Campus Box 8230, 660 South Euclid Avenue, St.Louis Missouri 63110-1093, USA. Phone: 314.286.1590; Email: khader@wustl.edu. Or to: Mihai G. Netea, Department of Internal Medicine, Radboud University, Medical Center, PO Box 9101, 6500HB, Nijmegen, Netherlands. Phone: 31.0.24.361.46.52; Email:mihai.netea@radboudumc.nl.

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1Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.

2Meakins-Christie Laboratories, Department of Medicine, Department of Microbiology and Immunology, and Department of Pathology, McGill International TB Centre, McGill University Health Centre, Montreal, Quebec, Canada.

3Bill & Melinda Gates Foundation, Seattle, Washington, USA.

4Centre for International Health, Department of Preventive and Social Medicine, University of Otago Medical School, Dunedin, New Zealand.

5Department of Oncology/Haematology, Krankenhaus Nordwest (KHNW), Frankfurt, Germany,

6ImmunoSurgery Unit, Champalimaud Foundation, Lisbon, Portugal.

7Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.

8Division of Chemical Systems & Synthetic Biology, Institute for Infectious Disease & Molecular Medicine (IDM), Faculty of Health Sciences, Department of Integrative Biomedical Sciences, and

9South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.

10Texas Biomedical Research Institute, San Antonio, Texas, USA.

11Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.

12Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.

13Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

14Center for Computational and Integrative Biology and

15Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

16Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

17Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.

18The Working Group is detailed in Supplemental Acknowledgments.

Address correspondence to: Shabaana A. Khader, Department of Molecular Microbiology, Washington University in St.Louis, Campus Box 8230, 660 South Euclid Avenue, St.Louis Missouri 63110-1093, USA. Phone: 314.286.1590; Email: khader@wustl.edu. Or to: Mihai G. Netea, Department of Internal Medicine, Radboud University, Medical Center, PO Box 9101, 6500HB, Nijmegen, Netherlands. Phone: 31.0.24.361.46.52; Email:mihai.netea@radboudumc.nl.

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1Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.

2Meakins-Christie Laboratories, Department of Medicine, Department of Microbiology and Immunology, and Department of Pathology, McGill International TB Centre, McGill University Health Centre, Montreal, Quebec, Canada.

3Bill & Melinda Gates Foundation, Seattle, Washington, USA.

4Centre for International Health, Department of Preventive and Social Medicine, University of Otago Medical School, Dunedin, New Zealand.

5Department of Oncology/Haematology, Krankenhaus Nordwest (KHNW), Frankfurt, Germany,

6ImmunoSurgery Unit, Champalimaud Foundation, Lisbon, Portugal.

7Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.

8Division of Chemical Systems & Synthetic Biology, Institute for Infectious Disease & Molecular Medicine (IDM), Faculty of Health Sciences, Department of Integrative Biomedical Sciences, and

9South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.

10Texas Biomedical Research Institute, San Antonio, Texas, USA.

11Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.

12Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.

13Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

14Center for Computational and Integrative Biology and

15Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

16Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

17Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.

18The Working Group is detailed in Supplemental Acknowledgments.

Address correspondence to: Shabaana A. Khader, Department of Molecular Microbiology, Washington University in St.Louis, Campus Box 8230, 660 South Euclid Avenue, St.Louis Missouri 63110-1093, USA. Phone: 314.286.1590; Email: khader@wustl.edu. Or to: Mihai G. Netea, Department of Internal Medicine, Radboud University, Medical Center, PO Box 9101, 6500HB, Nijmegen, Netherlands. Phone: 31.0.24.361.46.52; Email:mihai.netea@radboudumc.nl.

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1Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.

2Meakins-Christie Laboratories, Department of Medicine, Department of Microbiology and Immunology, and Department of Pathology, McGill International TB Centre, McGill University Health Centre, Montreal, Quebec, Canada.

3Bill & Melinda Gates Foundation, Seattle, Washington, USA.

4Centre for International Health, Department of Preventive and Social Medicine, University of Otago Medical School, Dunedin, New Zealand.

5Department of Oncology/Haematology, Krankenhaus Nordwest (KHNW), Frankfurt, Germany,

6ImmunoSurgery Unit, Champalimaud Foundation, Lisbon, Portugal.

7Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.

8Division of Chemical Systems & Synthetic Biology, Institute for Infectious Disease & Molecular Medicine (IDM), Faculty of Health Sciences, Department of Integrative Biomedical Sciences, and

9South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.

10Texas Biomedical Research Institute, San Antonio, Texas, USA.

11Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.

12Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.

13Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

14Center for Computational and Integrative Biology and

15Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

16Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

17Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.

18The Working Group is detailed in Supplemental Acknowledgments.

Address correspondence to: Shabaana A. Khader, Department of Molecular Microbiology, Washington University in St.Louis, Campus Box 8230, 660 South Euclid Avenue, St.Louis Missouri 63110-1093, USA. Phone: 314.286.1590; Email: khader@wustl.edu. Or to: Mihai G. Netea, Department of Internal Medicine, Radboud University, Medical Center, PO Box 9101, 6500HB, Nijmegen, Netherlands. Phone: 31.0.24.361.46.52; Email:mihai.netea@radboudumc.nl.

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1Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.

2Meakins-Christie Laboratories, Department of Medicine, Department of Microbiology and Immunology, and Department of Pathology, McGill International TB Centre, McGill University Health Centre, Montreal, Quebec, Canada.

3Bill & Melinda Gates Foundation, Seattle, Washington, USA.

4Centre for International Health, Department of Preventive and Social Medicine, University of Otago Medical School, Dunedin, New Zealand.

5Department of Oncology/Haematology, Krankenhaus Nordwest (KHNW), Frankfurt, Germany,

6ImmunoSurgery Unit, Champalimaud Foundation, Lisbon, Portugal.

7Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.

8Division of Chemical Systems & Synthetic Biology, Institute for Infectious Disease & Molecular Medicine (IDM), Faculty of Health Sciences, Department of Integrative Biomedical Sciences, and

9South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.

10Texas Biomedical Research Institute, San Antonio, Texas, USA.

11Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.

12Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.

13Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

14Center for Computational and Integrative Biology and

15Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

16Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

17Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.

18The Working Group is detailed in Supplemental Acknowledgments.

Address correspondence to: Shabaana A. Khader, Department of Molecular Microbiology, Washington University in St.Louis, Campus Box 8230, 660 South Euclid Avenue, St.Louis Missouri 63110-1093, USA. Phone: 314.286.1590; Email: khader@wustl.edu. Or to: Mihai G. Netea, Department of Internal Medicine, Radboud University, Medical Center, PO Box 9101, 6500HB, Nijmegen, Netherlands. Phone: 31.0.24.361.46.52; Email:mihai.netea@radboudumc.nl.

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1Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.

2Meakins-Christie Laboratories, Department of Medicine, Department of Microbiology and Immunology, and Department of Pathology, McGill International TB Centre, McGill University Health Centre, Montreal, Quebec, Canada.

3Bill & Melinda Gates Foundation, Seattle, Washington, USA.

4Centre for International Health, Department of Preventive and Social Medicine, University of Otago Medical School, Dunedin, New Zealand.

5Department of Oncology/Haematology, Krankenhaus Nordwest (KHNW), Frankfurt, Germany,

6ImmunoSurgery Unit, Champalimaud Foundation, Lisbon, Portugal.

7Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.

8Division of Chemical Systems & Synthetic Biology, Institute for Infectious Disease & Molecular Medicine (IDM), Faculty of Health Sciences, Department of Integrative Biomedical Sciences, and

9South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.

10Texas Biomedical Research Institute, San Antonio, Texas, USA.

11Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.

12Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.

13Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

14Center for Computational and Integrative Biology and

15Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

16Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

17Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.

18The Working Group is detailed in Supplemental Acknowledgments.

Address correspondence to: Shabaana A. Khader, Department of Molecular Microbiology, Washington University in St.Louis, Campus Box 8230, 660 South Euclid Avenue, St.Louis Missouri 63110-1093, USA. Phone: 314.286.1590; Email: khader@wustl.edu. Or to: Mihai G. Netea, Department of Internal Medicine, Radboud University, Medical Center, PO Box 9101, 6500HB, Nijmegen, Netherlands. Phone: 31.0.24.361.46.52; Email:mihai.netea@radboudumc.nl.

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1Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.

2Meakins-Christie Laboratories, Department of Medicine, Department of Microbiology and Immunology, and Department of Pathology, McGill International TB Centre, McGill University Health Centre, Montreal, Quebec, Canada.

3Bill & Melinda Gates Foundation, Seattle, Washington, USA.

4Centre for International Health, Department of Preventive and Social Medicine, University of Otago Medical School, Dunedin, New Zealand.

5Department of Oncology/Haematology, Krankenhaus Nordwest (KHNW), Frankfurt, Germany,

6ImmunoSurgery Unit, Champalimaud Foundation, Lisbon, Portugal.

7Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.

8Division of Chemical Systems & Synthetic Biology, Institute for Infectious Disease & Molecular Medicine (IDM), Faculty of Health Sciences, Department of Integrative Biomedical Sciences, and

9South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.

10Texas Biomedical Research Institute, San Antonio, Texas, USA.

11Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.

12Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.

13Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

14Center for Computational and Integrative Biology and

15Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

16Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

17Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.

18The Working Group is detailed in Supplemental Acknowledgments.

Address correspondence to: Shabaana A. Khader, Department of Molecular Microbiology, Washington University in St.Louis, Campus Box 8230, 660 South Euclid Avenue, St.Louis Missouri 63110-1093, USA. Phone: 314.286.1590; Email: khader@wustl.edu. Or to: Mihai G. Netea, Department of Internal Medicine, Radboud University, Medical Center, PO Box 9101, 6500HB, Nijmegen, Netherlands. Phone: 31.0.24.361.46.52; Email:mihai.netea@radboudumc.nl.

Find articles by Xavier, R. in: JCI | PubMed | Google Scholar |

1Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.

2Meakins-Christie Laboratories, Department of Medicine, Department of Microbiology and Immunology, and Department of Pathology, McGill International TB Centre, McGill University Health Centre, Montreal, Quebec, Canada.

3Bill & Melinda Gates Foundation, Seattle, Washington, USA.

4Centre for International Health, Department of Preventive and Social Medicine, University of Otago Medical School, Dunedin, New Zealand.

5Department of Oncology/Haematology, Krankenhaus Nordwest (KHNW), Frankfurt, Germany,

6ImmunoSurgery Unit, Champalimaud Foundation, Lisbon, Portugal.

7Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.

8Division of Chemical Systems & Synthetic Biology, Institute for Infectious Disease & Molecular Medicine (IDM), Faculty of Health Sciences, Department of Integrative Biomedical Sciences, and

9South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.

10Texas Biomedical Research Institute, San Antonio, Texas, USA.

11Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.

12Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.

13Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

14Center for Computational and Integrative Biology and

15Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

16Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

17Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.

18The Working Group is detailed in Supplemental Acknowledgments.

Address correspondence to: Shabaana A. Khader, Department of Molecular Microbiology, Washington University in St.Louis, Campus Box 8230, 660 South Euclid Avenue, St.Louis Missouri 63110-1093, USA. Phone: 314.286.1590; Email: khader@wustl.edu. Or to: Mihai G. Netea, Department of Internal Medicine, Radboud University, Medical Center, PO Box 9101, 6500HB, Nijmegen, Netherlands. Phone: 31.0.24.361.46.52; Email:mihai.netea@radboudumc.nl.

Find articles by Netea, M. in: JCI | PubMed | Google Scholar

1Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.

2Meakins-Christie Laboratories, Department of Medicine, Department of Microbiology and Immunology, and Department of Pathology, McGill International TB Centre, McGill University Health Centre, Montreal, Quebec, Canada.

3Bill & Melinda Gates Foundation, Seattle, Washington, USA.

4Centre for International Health, Department of Preventive and Social Medicine, University of Otago Medical School, Dunedin, New Zealand.

5Department of Oncology/Haematology, Krankenhaus Nordwest (KHNW), Frankfurt, Germany,

6ImmunoSurgery Unit, Champalimaud Foundation, Lisbon, Portugal.

7Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.

8Division of Chemical Systems & Synthetic Biology, Institute for Infectious Disease & Molecular Medicine (IDM), Faculty of Health Sciences, Department of Integrative Biomedical Sciences, and

9South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.

10Texas Biomedical Research Institute, San Antonio, Texas, USA.

11Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.

12Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.

13Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

14Center for Computational and Integrative Biology and

15Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

16Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

17Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.

18The Working Group is detailed in Supplemental Acknowledgments.

Address correspondence to: Shabaana A. Khader, Department of Molecular Microbiology, Washington University in St.Louis, Campus Box 8230, 660 South Euclid Avenue, St.Louis Missouri 63110-1093, USA. Phone: 314.286.1590; Email: khader@wustl.edu. Or to: Mihai G. Netea, Department of Internal Medicine, Radboud University, Medical Center, PO Box 9101, 6500HB, Nijmegen, Netherlands. Phone: 31.0.24.361.46.52; Email:mihai.netea@radboudumc.nl.

First published September 3, 2019 - More info

Published in Volume 129, Issue 9 on September 3, 2019
J Clin Invest. 2019;129(9):3482–3491. https://doi.org/10.1172/JCI128877.
© 2019 American Society for Clinical Investigation
First published September 3, 2019 - Version history

Vaccine development against tuberculosis (TB) is based on the induction of adaptive immune responses endowed with long-term memory against mycobacterial antigens. Memory B and T cells initiate a rapid and robust immune response upon encounter with Mycobacterium tuberculosis, thus achieving long-lasting protection against infection. Recent studies have shown, however, that innate immune cell populations such as myeloid cells and NK cells also undergo functional adaptation after infection or vaccination, a de facto innate immune memory that is also termed trained immunity. Experimental and epidemiological data have shown that induction of trained immunity contributes to the beneficial heterologous effects of vaccines such as bacille Calmette-Guérin (BCG), the licensed TB vaccine. Moreover, increasing evidence argues that trained immunity also contributes to the anti-TB effects of BCG vaccination. An interaction among immunological signals, metabolic rewiring, and epigenetic reprogramming underlies the molecular mechanisms mediating trained immunity in myeloid cells and their bone marrow progenitors. Future studies are warranted to explore the untapped potential of trained immunity to develop a future generation of TB vaccines that would combine innate and adaptive immune memory induction.

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