The IL-17A-neutrophil axis promotes epithelial cell IL-33 production during nematode lung migration

TY - JOUR

T1 - The IL-17A-neutrophil axis promotes epithelial cell IL-33 production during nematode lung migration

AU - Ajendra, Jesuthas

AU - Papotto, Pedro H.

AU - Parkinson, James E.

AU - Dodd, Rebecca J.

AU - Bombeiro, André L.

AU - Pearson, Stella

AU - Chan, Brian H. K.

AU - Ribot, Julie C.

AU - McSorley, Henry J.

AU - Sutherland, Tara E.

AU - Allen, Judith E.

N1 - Copyright: © 2023 The Author(s). Published by Elsevier Inc. on behalf of Society for Mucosal Immunology.

PY - 2023/12

Y1 - 2023/12

N2 - The early migratory phase of pulmonary helminth infections is characterized by tissue injury leading to the release of the alarmin interleukin (IL)-33 and subsequent induction of type 2 immune responses. We recently described a role for IL-17A, through suppression of interferon (IFN)-γ, as an important inducer of type 2 responses during infection with the lung-migrating rodent nematode Nippostrongylus brasiliensis. Here, we aimed to investigate the interaction between IL-17A and IL-33 during the early lung migratory stages of N. brasiliensis infection. In this brief report, we demonstrate that deficiency of IL-17A leads to impaired IL-33 expression and secretion early in infection, independent of IL-17A suppression of IFN-γ. Neutrophil-depletion experiments, which dramatically reduce lung injury, revealed that neutrophils are primarily responsible for the IL-17A-dependent release of IL-33 into the airways. Taken together, our results reveal an IL-17A-neutrophil-axis that can drive IL-33 during helminth infection, highlighting an additional pathway by which IL-17A regulates pulmonary type 2 immunity.

AB - The early migratory phase of pulmonary helminth infections is characterized by tissue injury leading to the release of the alarmin interleukin (IL)-33 and subsequent induction of type 2 immune responses. We recently described a role for IL-17A, through suppression of interferon (IFN)-γ, as an important inducer of type 2 responses during infection with the lung-migrating rodent nematode Nippostrongylus brasiliensis. Here, we aimed to investigate the interaction between IL-17A and IL-33 during the early lung migratory stages of N. brasiliensis infection. In this brief report, we demonstrate that deficiency of IL-17A leads to impaired IL-33 expression and secretion early in infection, independent of IL-17A suppression of IFN-γ. Neutrophil-depletion experiments, which dramatically reduce lung injury, revealed that neutrophils are primarily responsible for the IL-17A-dependent release of IL-33 into the airways. Taken together, our results reveal an IL-17A-neutrophil-axis that can drive IL-33 during helminth infection, highlighting an additional pathway by which IL-17A regulates pulmonary type 2 immunity.

UR - https://www.scopus.com/pages/publications/85175262686

U2 - 10.1016/j.mucimm.2023.09.006

DO - 10.1016/j.mucimm.2023.09.006

M3 - Article

C2 - 37783278

SN - 1933-0219

VL - 16

SP - 767

EP - 775

JO - Mucosal Immunology

JF - Mucosal Immunology

IS - 6

ER -