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Nature. 2019 Jun;570(7762):528-532. doi: 10.1038/s41586-019-1276-2. Epub 2019 Jun 5.

Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis.

Author information

1
Africa Health Research Institute, Durban, South Africa.
2
School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
3
Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO, USA.
4
Institute for Medical Engineering and Science, Department of Chemistry, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
5
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
6
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
7
Division of Allergy, Immmunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
8
Department of Tropical and Infectious Diseases, Institute of Primate Research, Nairobi, Kenya.
9
Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.
10
IDM, University of Cape Town, Cape Town, South Africa.
11
Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, MO, USA.
12
Department of Cardiothoracic Surgery, Nelson Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
13
Tulane National Primate Research Center, Covington, LA, USA.
14
Tulane University Health Sciences, New Orleans, LA, USA.
15
Department of Microbiology, Centres for AIDS Research and Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
16
Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico.
17
Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico.
18
Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
19
Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
20
Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
21
Department of Infection and Immunity, University College London, London, UK.
22
Africa Health Research Institute, Durban, South Africa. al.leslie@ahri.org.
23
School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa. al.leslie@ahri.org.
24
Department of Infection and Immunity, University College London, London, UK. al.leslie@ahri.org.
25
Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO, USA. sakhader@wustl.edu.

Abstract

Tuberculosis is the leading cause of death by an infectious disease worldwide1. However, the involvement of innate lymphoid cells (ILCs) in immune responses to infection with Mycobacterium tuberculosis (Mtb) is unknown. Here we show that circulating subsets of ILCs are depleted from the blood of participants with pulmonary tuberculosis and restored upon treatment. Tuberculosis increased accumulation of ILC subsets in the human lung, coinciding with a robust transcriptional response to infection, including a role in orchestrating the recruitment of immune subsets. Using mouse models, we show that group 3 ILCs (ILC3s) accumulated rapidly in Mtb-infected lungs and coincided with the accumulation of alveolar macrophages. Notably, mice that lacked ILC3s exhibited a reduction in the accumulation of early alveolar macrophages and decreased Mtb control. We show that the C-X-C motif chemokine receptor 5 (CXCR5)-C-X-C motif chemokine ligand 13 (CXCL13) axis is involved in Mtb control, as infection upregulates CXCR5 on circulating ILC3s and increases plasma levels of its ligand, CXCL13, in humans. Moreover, interleukin-23-dependent expansion of ILC3s in mice and production of interleukin-17 and interleukin-22 were found to be critical inducers of lung CXCL13, early innate immunity and the formation of protective lymphoid follicles within granulomas. Thus, we demonstrate an early protective role for ILC3s in immunity to Mtb infection.

PMID:
31168092
PMCID:
PMC6626542
[Available on 2019-12-05]
DOI:
10.1038/s41586-019-1276-2

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