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IL-17A both initiates, via IFNγ suppression, and limits the pulmonary type-2 immune response to nematode infection

Ajendra, Jesuthas, Chenery, Alistair L., Parkinson, James E., Chan, Brian H. K., Pearson, Stella, Colombo, Stefano, Boon, Louis, Grencis, Richard K., Sutherland, Tara E. and Allen, Judith E. (2020) 'IL-17A both initiates, via IFNγ suppression, and limits the pulmonary type-2 immune response to nematode infection'. Mucosal Immunology, Vol 13, Issue 6, pp. 958-968.

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Abstract

Nippostrongylus brasiliensis is a well-defined model of type-2 immunity but the early lung-migrating phase is dominated by innate IL-17A production. In this study, we confirm previous observations that Il17a-KO mice infected with N. brasiliensis exhibit an impaired type-2 immune response. Transcriptional profiling of the lung on day 2 of N. brasiliensis infection revealed an increased Ifng signature in Il17a-KO mice confirmed by enhanced IFNγ protein production in lung lymphocyte populations. Depletion of early IFNγ rescued type-2 immune responses in the Il17a-KO mice demonstrating that IL-17A-mediated suppression of IFNγ promotes type-2 immunity. Notably, later in infection, once the type-2 response was established, IL-17A limited the magnitude of the type-2 response. IL-17A regulation of type-2 immunity was lung-specific and infection with Trichuris muris revealed that IL-17A promotes a type-2 immune response in the lung even when infection is restricted to the intestine. Together our data reveal IL-17A as a major regulator of pulmonary type-2 immunity such that IL-17A supports early development of a protective type-2 response by suppression of IFNγ but subsequently limits excessive type-2 responses. A failure of this feedback loop may contribute to conditions such as severe asthma, characterised by combined elevation of IL-17 and type-2 cytokines.

Item Type: Article
Subjects: QW Microbiology and Immunology > Immunity by Type > QW 568 Cellular immunity. Immunologic cytotoxicity. Immunocompetence. Immunologic factors (General)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 695 Parasitic diseases (General)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 810 Schistosomiasis
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 850 Nematode infections (General)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 885 Onchocerciasis
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1038/s41385-020-0318-2
Depositing User: Cathy Waldron
Date Deposited: 09 Jul 2020 14:56
Last Modified: 29 Oct 2020 11:42
URI: https://archive.lstmed.ac.uk/id/eprint/14999

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