title: Signaling via the IL-20 receptor inhibits cutaneous production of IL-1β and IL-17A to promote infection with methicillin-resistant Staphylococcus aureus.
abstract: Staphylococcus aureus causes most infections of human skin and soft tissue and is a major infectious cause of mortality. Host defense mechanisms against S. aureus are incompletely understood. Interleukin 19 (IL-19), IL-20 and IL-24 signal through type I and type II IL-20 receptors and are associated with inflammatory skin diseases such as psoriasis and atopic dermatitis. We found here that those cytokines promoted cutaneous infection with S. aureus in mice by downregulating IL-1β- and IL-17A-dependent pathways. We noted similar effects of those cytokines in human keratinocytes after exposure to S. aureus, and antibody blockade of the IL-20 receptor improved outcomes in infected mice. Our findings identify an immunosuppressive role for IL-19, IL-20 and IL-24 during infection that could be therapeutically targeted to alter susceptibility to infection.
authors.affiliation: Bacterial Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Myles
authors.forename: Natalia M
authors.initials: NM
authors.lastname: Fontecilla
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Valdez
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Vithayathil
authors.forename: Shruti
authors.initials: S
authors.lastname: Naik
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ouyang
authors.forename: Sandip K
authors.initials: SK
authors.lastname: Datta
mesh_terms: D000818:Animals; D001706:Biopsy; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006651:Histocytochemistry; D006801:Humans; D015151:Immunoblotting; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology*; D015603:Keratinocytes; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013207:Staphylococcal Skin Infections / Q000276:immunology* / Q000382:microbiology*
chemical_list: D020381:Interleukin-17; D053583:Interleukin-1beta; D012329:RNA, Bacterial; D018123:Receptors, Interleukin; C492510:interleukin-20 receptor