AUTHOR=Johnson M. Brittany , Furr Kelli H. , Suptela Samantha R. , Leach Whitney , Marriott Ian 

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

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.1066237

DOI=10.3389/fmicb.2022.1066237

ISSN=1664-302X

ABSTRACT=The refractory and recurrent nature of chronic staphylococcal osteomyelitis may be due, at least in part, to the ability of Staphylococcus aureus to invade and persist within bone-forming osteoblasts.  However, osteoblasts are now recognized to respond to S. aureus infection to 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 S. aureus.  Here, we report the presence of markedly elevated IFN-beta levels in infected bone tissue in a mouse model of staphylococcal osteomyelitis.  RNA Tag-Seq analysis of S. aureus infected primary murine osteoblasts showed enrichment of genes associated with type I IFN signaling and IFN stimulated genes (ISGs), and elevated expression of mRNA encoding IFN-beta and ISG products.  IFN-beta production was confirmed with the demonstration that S. aureus induces its rapid and robust release by osteoblasts in a dose-dependent manner.  Furthermore, we show increased protein expression of the ISG products IFIT1 and IFIT3 by infected osteoblasts and demonstrate that this occurs secondary to the release of IFN-beta by these cells.  Finally, we have determined that exposure of S. aureus-infected osteoblasts to IFN-beta 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-beta that can act in an autocrine and/or paracrine manner to elicit ISG expression and mitigate S. aureus infection.