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Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis

Ardain, A; Domingo-Gonzalez, R; Das, S; Kazer, SW; Howard, NC; Singh, A; Ahmed, M; ... Khader, SA; + view all (2019) Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis. Nature , 570 (7762) pp. 528-532. 10.1038/s41586-019-1276-2. Green open access

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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.

Type: Article
Title: Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41586-019-1276-2
Publisher version: https://doi.org/10.1038/s41586-019-1276-2
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, ONCOSTATIN-M, INFLAMMATION, INFECTION, RESPONSES, RECEPTOR, PRECURSORS, EXPRESSION, DECTIN-1, IL-17, GENE
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10082075
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