PT  - JOURNAL ARTICLE
AU  - Jesuthas Ajendra
AU  - Alistair L. Chenery
AU  - James E. Parkinson
AU  - Brian H. K. Chan
AU  - Stella Pearson
AU  - Stefano A. P. Colombo
AU  - Louis Boon
AU  - Richard K. Grencis
AU  - Tara E. Sutherland
AU  - Judith E. Allen
TI  - IL-17A both initiates (via IFNγ suppression) and limits the pulmonary type-2 immune response to nematode infection
AID  - 10.1101/827899
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 827899
4099  - http://biorxiv.org/content/early/2020/04/18/827899.short
4100  - http://biorxiv.org/content/early/2020/04/18/827899.full
AB  - Nippostrongylus brasiliensis is a well-defined model of type-2 immunity but the early lung-migrating phase is dominated by innate IL-17A production and neutrophilia. Using N. brasiliensis infection we confirm previous observations that Il17a-KO mice exhibit an impaired type-2 immune response. Neutrophil depletion and reconstitution studies demonstrated that neutrophils contribute to the subsequent eosinophilia but are not responsible for the ability of IL-17A to promote type-2 cytokine responses. Transcriptional profiling of the lung on day 2 of N. brasiliensis infection revealed an increased Ifnγ signature in the Il17a-KO mice confirmed by enhanced IFNγ protein production. 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, when IL-17A was blocked later in infection, the type-2 response increased. 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 a parasite lifecycle is restricted to the intestine. Together our data reveal IL-17A as a major regulator of pulmonary type-2 immunity which supports the development of a protective type-2 immune response but subsequently limits the magnitude of that response.Competing Interest StatementThe authors have declared no competing interest.