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.
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Journal of Virology, American Society for Microbiology, 2013, 87 (12), pp.6911-24. 〈10.1128/JVI.02943-12〉
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Contributeur : Jean-Claude Sirard <>
Soumis le : jeudi 9 janvier 2014 - 22:05:18
Dernière modification le : lundi 5 février 2018 - 15:22:12

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Stoyan Ivanov, Joelle Renneson, Josette Fontaine, Adeline Barthelemy, Christophe Paget, et al.. Interleukin-22 reduces lung inflammation during influenza A virus infection and protects against secondary bacterial infection.. Journal of Virology, American Society for Microbiology, 2013, 87 (12), pp.6911-24. 〈10.1128/JVI.02943-12〉. 〈inserm-00926618〉

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