• Stoyan Ivanov, Joelle Renneson, Josette Fontaine, Adeline Barthelemy, Christophe Paget, Elodie Macho Fernandez, Fany Blanc, Carl De Trez, Laurye Van Maele, Laure Dumoutier, Michel-René Huerre, Gérard Eberl, Mustapha Si-Tahar, Pierre Gosset, Jean Christophe Renauld, Jean Claude Sirard, Christelle Faveeuw, and François Trottein.
• Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, Lille, France.
• J. Virol. 2013 Jun 1; 87 (12): 6911-24.

AbstractInterleukin-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.

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