title: Failure to induce IFN-β production during Staphylococcus aureus infection contributes to pathogenicity.
abstract: The importance of type I IFNs in the host response to viral infection is well established; however, their role in bacterial infection is not fully understood. Several bacteria (both Gram-positive and -negative) have been shown to induce IFN-β production in myeloid cells, but this IFN-β is not always beneficial to the host. We examined whether Staphylococcus aureus induces IFN-β from myeloid phagocytes, and if so, whether it is helpful or harmful to the host to do so. We found that S. aureus poorly induces IFN-β production compared with other bacteria. S. aureus is highly resistant to degradation in the phagosome because it is resistant to lysozyme. Using a mutant that is more sensitive to lysozyme, we show that phagosomal degradation and release of intracellular ligands is essential for induction of IFN-β and inflammatory chemokines downstream of IFN-β. Further, we found that adding exogenous IFN-β during S. aureus infection (in vitro and in vivo) was protective. Together, the data demonstrate that failure to induce IFN-β production during S. aureus infection contributes to pathogenicity.
authors.affiliation: Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Kaplan
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Pierre
authors.initials: P
authors.lastname: Kyme
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Wolf
authors.forename: Courtney A
authors.initials: CA
authors.lastname: Becker
authors.forename: Ching Wen
authors.initials: CW
authors.lastname: Tseng
authors.forename: George Y
authors.initials: GY
authors.lastname: Liu
authors.forename: David M
authors.initials: DM
authors.lastname: Underhill
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D016899:Interferon-beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000276:immunology; D013203:Staphylococcal Infections / Q000097:blood / Q000276:immunology* / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*
chemical_list: D016899:Interferon-beta