IL-36γ Protects against Severe Influenza Infection by Promoting Lung Alveolar Macrophage Survival and Limiting Viral Replication

The Journal of Immunology : Official Journal of the American Association of Immunologists
Alexander N WeinJacob E Kohlmeier

Abstract

Although influenza virus infection remains a concerning disease for public health, the roles of individual cytokines during the immune response to influenza infection are not fully understood. We have identified IL-36γ as a key mediator of immune protection during both high- and low-pathogenesis influenza infection. Il36g mRNA is upregulated in the lung following influenza infection, and mice lacking IL-36γ have greatly increased morbidity and mortality upon infection with either H1N1 or H3N2 influenza. The increased severity of influenza infection in IL-36γ-knockout (KO) mice is associated with increased viral titers, higher levels of proinflammatory cytokines early in infection, and more diffuse pathologic conditions late in the disease course. Interestingly, the increased severity of disease in IL-36γ-KO mice correlates with a rapid loss of alveolar macrophages following infection. We find that the alveolar macrophages from naive IL-36γ-KO mice have higher expression of M2-like surface markers compared with wild-type (WT) mice and show increased apoptosis within 24 h of infection. Finally, transfer of WT alveolar macrophages to IL-36γ-KO mice restores protection against lethal influenza challenge to levels observed in WT mic...Continue Reading

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Citations

Dec 24, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Caroline M PercopoHelene F Rosenberg
Nov 13, 2019·Immunology·Elza EvrenTim Willinger
Feb 10, 2021·Communications Biology·Carolin K KossKarim C El Kasmi
Jan 28, 2021·Immunology·Vu L NgoTimothy L Denning
Sep 9, 2020·Cellular Signalling·Yingying HanAndreas Weigert
Jun 1, 2021·Frontiers in Immunology·Xiaofang WangYuejin Liang
Aug 9, 2021·Cellular and Molecular Life Sciences : CMLS·James ByrneElizabeth Brint
Jan 21, 2022·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xiaofang WangJiaren Sun

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