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

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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. (In Press)

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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: 03 Aug 2020 09:35
URI: https://archive.lstmed.ac.uk/id/eprint/14999

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