Influenza A/PR8 virus infection in mice suppresses basal and Oncostatin M-induced IL-33 expression in vivo and in vitro.

Influenza A virus (IAV) infection typically induces both innate and adaptive immune mechanisms. IL-33, an "alarmin" cytokine with pro-inflammatory effects, may have roles in IAV infection. IL-33 can be upregulated by the gp130 cytokine Oncostatin M (OSM), which induces Th2-skewed inflammation (eosinophils, Arg1 + Macrophages, IL-33, IL-4, eotaxin-2) in mouse lungs. We here examined both OSM and IL-33 regulation by the IAV-H1N1/PR8 strain. Female C57BL/6 mice infected intranasally with H1N1/PR8 showed time-dependent elevation of OSM expression but a reduction in lung IL-33 protein and mRNA. Since this suggested active suppression of IL-33 by H1N1/PR8, we assessed H1N1/PR8 superinfection in mice with established Th2-skewed inflammation induced by Adenoviral vector overexpressing OSM administered 7 days prior. H1N1/PR8 markedly reduced eosinophil and Arg1 + macrophage accumulation, IL-33, IL-4, and eotaxin-2 expression 5-days post infection. IFNγ partially inhibited OSM-induced IL-33 protein in mouse lung epithelial (C10) cells in vitro, and both basal and OSM-induced IL-33 expression were markedly suppressed by direct H1N1/PR8 infection of C10 cells, whereas TIMP-1 or OSMRβ were not. Collectively, IL-33 was selectively suppressed by H1N1/PR8 infection in part by direct effects of virus on IL-33-expressing epithelial cells. Thus, although influenza infection induces OSM, IAV also selectively suppresses IL-33 and IL-33-mediated downstream Th2-skewed inflammation.