Induction of protective interferon-β responses in murine osteoblasts following Staphylococcus aureus infection

The refractory and recurrent nature of chronic staphylococcal osteomyelitis may be due, at least in part, to the ability of to invade and persist within bone-forming osteoblasts. However, osteoblasts are now recognized to respond to . infection and produce numerous immune mediators and bone regulatory factors that can shape the host response. Type I interferons (IFNs) are best known for their antiviral effects, but it is becoming apparent that they impact host susceptibility to a wide range of pathogens including . . Here, we have assessed the local expression of IFN-β by specific capture ELISA in an established in vivo mouse model of staphylococcal osteomyelitis. RNA Tag-Seq analysis, specific capture ELISAs, and/or immunoblot analyses, were then used to assess the expression of type I IFNs and select IFN stimulated genes (ISGs) in . infected primary murine osteoblasts. The effect of IFN-β on intracellular . burden was assessed in vitro following recombinant cytokine treatment by serial colony counts of liberated bacteria. We report the presence of markedly elevated IFN-β levels in infected bone tissue in a mouse model of staphylococcal osteomyelitis. RNA Tag-Seq analysis of . infected osteoblasts showed enrichment of genes associated with type I IFN signaling and ISGs, and elevated expression of mRNA encoding IFN-β and ISG products. IFN-β production was confirmed with the demonstration that . induces its rapid and robust release by osteoblasts in a dose-dependent manner. Furthermore, we showed increased protein expression of the ISG products IFIT1 and IFIT3 by infected osteoblasts and demonstrate that this occurs secondary to the release of IFN-β by these cells. Finally, we have determined that exposure of . -infected osteoblasts to IFN-β markedly reduces the number of viable bacteria harbored by these cells. Together, these findings indicate an ability of osteoblasts to respond to bacteria by producing IFN-β that can act in an autocrine and/or paracrine manner to elicit ISG expression and mitigate . infection.