Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis
Name
nihms-1529144.pdf
Description
Accepted version
Size
5.57 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Ardain, Amanda
Domingo-Gonzalez, Racquel
Das, Shibali
Kazer, Samuel Weisgurt
Howard, Nicole C.
Singh, Alveera
Ahmed, Mushtaq
Nhamoyebonde, Shepherd
Rangel-Moreno, Javier
Ogongo, Paul
Date Issued
June 2019
Journal
Nature
Publisher
Springer Science+Business Media
Citation
Ardain, Amanda et al. "Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis." Nature, 570 (June 2019): 528-532 © 2019, The Author(s), under exclusive licence to Springer Nature Limited.
Version
Author's final manuscript
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. Keywords: Innate lymphoid cells; Tuberculosis
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Chemistry
Ragon Institute of MGH, MIT and Harvard
Broad Institute of MIT and Harvard
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/s41586-019-1276-2
