title: Infection with influenza virus induces IL-33 in murine lungs.
abstract: IL-33, a novel IL-1 family member, is crucially expressed and involved in pulmonary diseases, but its regulation in viral diseases such as influenza A virus (IAV) remains unclear. This study aimed to characterize the expression and release of IL-33 in lungs of IAV-infected mice in vivo and in murine respiratory epithelial cells (MLE-15) in vitro. Our results provide evidence of up-regulation of IL-33 mRNA in IAV-infected murine lungs, compared with noninfected control mice. The overexpression of IL-33 was positively correlated with a significant increase in mRNA encoding the proinflammatory cytokines TNF-α, IFN-γ, IL-1β, and IL-6, and was also associated with an increase in IFN-β mRNA. A profound overexpression of IL-33 protein was evident in IAV-infected murine lungs and bronchoalveolar lavages of influenza-infected mice, compared with low concentrations in naive lungs in vivo. Immunolocalization highlighted the cellular expression of IL-33 in alveolar epithelial and endothelial cells, along with increased infiltrate cells in virus-infected lungs. Further in vitro experiments showed an induction of IL-33 transcript-in MLE-15 cells and human epithelial cells (A549) infected with different strains of IAV in comparison with noninfected cells. In conclusion, our findings evidenced a profound expression of IL-33 in lungs during both in vivo and in vitro IAV infections, suggesting a role for IL-33 in virus-induced lung infections.
authors.affiliation: Unité de Virologie et Immunologie Moléculaires, Unité de Recherche, Institut National de la Recherche Agronomique, Jouy-en-Josas, France.
authors.forename: Ronan
authors.initials: R
authors.lastname: Le Goffic
authors.forename: Muhammad Imran
authors.initials: MI
authors.lastname: Arshad
authors.forename: Michel
authors.initials: M
authors.lastname: Rauch
authors.forename: Annie
authors.initials: A
authors.lastname: L'Helgoualc'h
authors.forename: Bernard
authors.initials: B
authors.lastname: Delmas
authors.forename: Claire
authors.initials: C
authors.lastname: Piquet-Pellorce
authors.forename: Michel
authors.initials: M
authors.lastname: Samson
mesh_terms: D000818:Animals; D018893:Bronchoalveolar Lavage; D002460:Cell Line; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000378:metabolism; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology* / Q000378:metabolism; D016899:Interferon-beta / Q000096:biosynthesis / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology; D000067596:Interleukin-33; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: C506535:Il33 protein, mouse; D053583:Interleukin-1beta; D000067596:Interleukin-33; D015850:Interleukin-6; D007378:Interleukins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D007371:Interferon-gamma