title: Interleukin-22 is produced by invariant natural killer T lymphocytes during influenza A virus infection: potential role in protection against lung epithelial damages.
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.
authors.affiliation: Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Paget
authors.forename: Stoyan
authors.initials: S
authors.lastname: Ivanov
authors.forename: Josette
authors.initials: J
authors.lastname: Fontaine
authors.forename: Joelle
authors.initials: J
authors.lastname: Renneson
authors.forename: Fany
authors.initials: F
authors.lastname: Blanc
authors.forename: Muriel
authors.initials: M
authors.lastname: Pichavant
authors.forename: Laure
authors.initials: L
authors.lastname: Dumoutier
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Jean Christophe
authors.initials: JC
authors.lastname: Renauld
authors.forename: Philippe
authors.initials: P
authors.lastname: Gosset
authors.forename: Pierre
authors.initials: P
authors.lastname: Gosset
authors.forename: Mustapha
authors.initials: M
authors.lastname: Si-Tahar
authors.forename: Christelle
authors.initials: C
authors.lastname: Faveeuw
authors.forename: François
authors.initials: F
authors.lastname: Trottein
mesh_terms: D000818:Animals; D016923:Cell Death; D004847:Epithelial Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology / Q000502:physiology*; D007251:Influenza, Human / Q000276:immunology* / Q000503:physiopathology* / Q000821:virology; D007378:Interleukins / Q000276:immunology*; D008168:Lung / Q000166:cytology* / Q000276:immunology / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology*; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D000097043:Interleukin-22