Staphylococcus aureus lipoproteins augment inflammatory responses in poly I:C-primed macrophages

Abstract

Secondary bacterial infection contributes to severe inflammation following viral infection. Among foodborne pathogenic bacteria, Staphylococcus aureus is known to exacerbate severe inflammatory responses after infection with single-stranded RNA viruses such as influenza viruses. However, it has not been determined if S. aureus infection enhances inflammatory responses after infection with RNA enteric viruses, including rotavirus, which is a double-stranded RNA virus. We therefore investigated the molecular mechanisms by which a cell wall component of S. aureus enhanced inflammatory responses during enteric viral infection using poly I:C-primed macrophages, which is a well-established model for double-stranded RNA virus infection. S. aureus lipoproteins enhanced IL-6 as well as TNF-alpha production in poly I:C-primed macrophages. Pam2CSK4, a mimic of Gram-positive bacterial lipoproteins and S. aureus lipoproteins, also significantly enhanced IL-6 production in poly I:C-primed macrophages. While IFN-beta expression was increased in poly I:C-primed macrophages treated with Pam2CSK4 or S. aureus lipoproteins, the level of IL-6 enhancement in poly I:C-primed macrophages was decreased in the presence of anti-IFN-alpha/beta receptor antibody, suggesting that IFN-beta plays an important role in enhanced IL-6 production. Phosphatidylinositol-3-kinase, Akt, ERK and NF-kappa B were also involved in the enhanced IL-6 production. Collectively, these results suggest that S. aureus lipoproteins induce excessive inflammatory responses in the presence of poly I:C.