title: Interleukin-22 reduces lung inflammation during influenza A virus infection and protects against secondary bacterial infection.
abstract: Interleukin-22 (IL-22) has redundant, protective, or pathogenic functions during autoimmune, inflammatory, and infectious diseases. Here, we addressed the potential role of IL-22 in host defense and pathogenesis during lethal and sublethal respiratory H3N2 influenza A virus (IAV) infection. We show that IL-22, as well as factors associated with its production, are expressed in the lung tissue during the early phases of IAV infection. Our data indicate that retinoic acid receptor-related orphan receptor-γt (RORγt)-positive αβ and γδ T cells, as well as innate lymphoid cells, expressed enhanced Il22 transcripts as early as 2 days postinfection. During lethal or sublethal IAV infections, endogenous IL-22 played no role in the control of IAV replication and in the development of the IAV-specific CD8(+) T cell response. During lethal infection, where wild-type (WT) mice succumbed to severe pneumonia, the lack of IL-22 did not accelerate or delay IAV-associated pathogenesis and animal death. In stark contrast, during sublethal IAV infection, IL-22-deficient animals had enhanced lung injuries and showed a lower airway epithelial integrity relative to WT littermates. Of importance, the protective effect of endogenous IL-22 in pulmonary damages was associated with a more controlled secondary bacterial infection. Indeed, after challenge with Streptococcus pneumoniae, IAV-experienced Il22(-/-) animals were more susceptible than WT controls in terms of survival rate and bacterial burden in the lungs. Together, IL-22 plays no major role during lethal influenza but is beneficial during sublethal H3N2 IAV infection, where it limits lung inflammation and subsequent bacterial superinfections.
authors.affiliation: Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, Lille, France.
authors.forename: Stoyan
authors.initials: S
authors.lastname: Ivanov
authors.forename: Joelle
authors.initials: J
authors.lastname: Renneson
authors.forename: Josette
authors.initials: J
authors.lastname: Fontaine
authors.forename: Adeline
authors.initials: A
authors.lastname: Barthelemy
authors.forename: Christophe
authors.initials: C
authors.lastname: Paget
authors.forename: Elodie Macho
authors.initials: EM
authors.lastname: Fernandez
authors.forename: Fany
authors.initials: F
authors.lastname: Blanc
authors.forename: Carl
authors.initials: C
authors.lastname: De Trez
authors.forename: Laurye
authors.initials: L
authors.lastname: Van Maele
authors.forename: Laure
authors.initials: L
authors.lastname: Dumoutier
authors.forename: Michel-René
authors.initials: MR
authors.lastname: Huerre
authors.forename: Gérard
authors.initials: G
authors.lastname: Eberl
authors.forename: Mustapha
authors.initials: M
authors.lastname: Si-Tahar
authors.forename: Pierre
authors.initials: P
authors.lastname: Gosset
authors.forename: Jean Christophe
authors.initials: JC
authors.lastname: Renauld
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Sirard
authors.forename: Christelle
authors.initials: C
authors.lastname: Faveeuw
authors.forename: François
authors.initials: F
authors.lastname: Trottein
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000276:immunology* / Q000382:microbiology; D060085:Coinfection / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology / Q000472:pathogenicity*; D007378:Interleukins / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000401:mortality / Q000821:virology; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D012141:Respiratory Tract Infections / Q000276:immunology / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000472:pathogenicity; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D000097043:Interleukin-22