title: Staphlyococcus aureus phenol-soluble modulins stimulate the release of proinflammatory cytokines from keratinocytes and are required for induction of skin inflammation.
abstract: Staphylococcus aureus is a human commensal that colonizes the skin. While it is normally innocuous, it has strong associations with atopic dermatitis pathogenesis and has become the leading cause of skin and soft tissue infections in the United States. The factors that dictate the role of S. aureus in disease are still being determined. In this work, we utilized primary keratinocyte culture and an epidermal murine colonization model to investigate the role of S. aureus phenol-soluble modulins (PSMs) in proinflammatory cytokine release and inflammation induction. We demonstrated that many species of Staphylococcus are capable of causing release of interleukin 18 (IL-18) from keratinocytes and that S. aureus PSMs are necessary and sufficient to stimulate IL-18 release from keratinocytes independently of caspase 1. Further, after 7 days of epicutaneous exposure to wild-type S. aureus, but not S. aureus Δpsm, we saw dramatic changes in gross pathology, as well as systemic release of proinflammatory cytokines. This work demonstrates the importance of PSM peptides in S. aureus-mediated inflammatory cytokine release from keratinocytes in vitro and in vivo and further implicates PSMs as important contributors to pathogenesis.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Adnan K
authors.initials: AK
authors.lastname: Syed
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Tamra J
authors.initials: TJ
authors.lastname: Reed
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Kaitlyn L
authors.initials: KL
authors.lastname: Clark
authors.affiliation: Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Blaise R
authors.initials: BR
authors.lastname: Boles
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, Michigan, USA mkahlenb@med.umich.edu.
authors.forename: J Michelle
authors.initials: JM
authors.lastname: Kahlenberg
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D003872:Dermatitis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020382:Interleukin-18 / Q000096:biosynthesis*; D015603:Keratinocytes / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D013207:Staphylococcal Skin Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology
chemical_list: D001427:Bacterial Toxins; D016207:Cytokines; D020382:Interleukin-18; C025971:staphylococcal delta toxin