{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T01:07:33Z","timestamp":1785892053887,"version":"3.56.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T00:00:00Z","timestamp":1669939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR074102"],"award-info":[{"award-number":["AR074102"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The refractory and recurrent nature of chronic staphylococcal osteomyelitis may be due, at least in part, to the ability of <jats:italic>Staphylococcus aureus<\/jats:italic> to invade and persist within bone-forming osteoblasts. However, osteoblasts are now recognized to respond to <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> 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 <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we have assessed the local expression of IFN-\u03b2 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 <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> infected primary murine osteoblasts. The effect of IFN-\u03b2 on intracellular <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> burden was assessed in vitro following recombinant cytokine treatment by serial colony counts of liberated bacteria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We report the presence of markedly elevated IFN-\u03b2 levels in infected bone tissue in a mouse model of staphylococcal osteomyelitis. RNA Tag-Seq analysis of <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> infected osteoblasts showed enrichment of genes associated with type I IFN signaling and ISGs, and elevated expression of mRNA encoding IFN-\u03b2 and ISG products. IFN-\u03b2 production was confirmed with the demonstration that <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> 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-\u03b2 by these cells. Finally, we have determined that exposure of <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic>-infected osteoblasts to IFN-\u03b2 markedly reduces the number of viable bacteria harbored by these cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Together, these findings indicate an ability of osteoblasts to respond to bacteria by producing IFN-\u03b2 that can act in an autocrine and\/or paracrine manner to elicit ISG expression and mitigate <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> infection.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2022.1066237","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T04:44:17Z","timestamp":1669956257000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Induction of protective interferon-\u03b2 responses in murine osteoblasts following Staphylococcus aureus infection"],"prefix":"10.3389","volume":"13","author":[{"given":"M. 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