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Interleukin-22 Is Produced by Invariant Natural Killer T Lymphocytes during Influenza A Virus Infection

Abstract : Invariant natural killer T (iNKT) cells are non-conventional lipid-reactive αβ T lymphocytes that play a key role in host responses during viral infections, in particular through the swift production of cytokines. Their beneficial role during experimental influenza A virus (IAV) infection has recently been proposed, although the mechanisms involved remain elusive. Here we show that during in vivo IAV infection, mouse pulmonary iNKT cells produce IFN-γ and IL-22, a Th17-related cytokine critical in mucosal immunity. Although permissive to viral replication, IL-22 production by iNKT cells is not due to IAV infection per se of these cells but is indirectly mediated by IAV-infected dendritic cells (DCs). We show that activation of the viral RNA sensors TLR7 and RIG-I in DCs is important for triggering IL-22 secretion by iNKT cells, whereas the NOD-like receptors NOD2 and NLRP3 are dispensable. Invariant NKT cells respond to IL-1β and IL-23 provided by infected DCs independently of the CD1d molecule to release IL-22. In vitro, IL-22 protects IAV-infected airway epithelial cells against mortality but has no role on viral replication. Finally, during early IAV infection, IL-22 plays a positive role in the control of lung epithelial damages. Overall, IAV infection of DCs activates iNKT cells, providing a rapid source of IL-22 that might be beneficial to preserve the lung epithelium integrity.
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Contributor : Fany Blanc <>
Submitted on : Friday, March 26, 2021 - 5:21:47 PM
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Christophe Paget, Stoyan Ivanov, Josette Fontaine, Joelle Renneson, Fany Blanc, et al.. Interleukin-22 Is Produced by Invariant Natural Killer T Lymphocytes during Influenza A Virus Infection. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2012, 287 (12), pp.8816-8829. ⟨10.1074/jbc.M111.304758⟩. ⟨hal-03182702⟩



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