ZBP1 governs the inflammasome-independent IL-1α and neutrophil inflammation that play a dual role in anti-influenza virus immunity.
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| Abstract |
Influenza A virus (IAV) triggers the infected lung to produce IL-1 and recruit neutrophils. Unlike IL-1β, however, little is known about IL-1α in terms of its mechanism of induction, action and physiological relevance to the host immunity against IAV infection. In particular, whether Z-DNA-binding protein 1 (ZBP1), a key molecule for IAV-induced cell death, is involved in the IL-1α induction, neutrophil infiltration and the physiological outcome has not been elucidated. Here, we show in a murine model that the IAV-induced IL-1α is mediated solely by ZBP1, in an NLRP3-inflammasome-independent manner, and is required for the optimal IL-1β production followed by the formation of neutrophil extracellular traps (NETs). During IAV infection, ZBP1 displays a dual role in anti-IAV immune responses mediated by neutrophils, resulting in either protective or pathological outcomes in vivo. Thus, ZBP1-mediated IL-1α production is the key initial step of IAV-infected NETs, regulating the duality of the consequent lung inflammation.
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| Authors | Masatoshi Momota, Patrick Lelliott, Atsuko Kubo, Takato Kusakabe, Kouji Kobiyama, Etsushi Kuroda, Yumiko Imai, Shizuo Akira, Cevayir Coban, Ken J Ishii |
| Journal | International immunology (Int Immunol) Vol. 32 Issue 3 Pg. 203-212 (03 07 2020) ISSN: 1460-2377 [Electronic] England |
| PMID | 31630209 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | © The Author(s) 2019. Published by Oxford University Press on behalf of The Japanese Society for Immunology. |
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