title: Interleukin-17A during local and systemic Staphylococcus aureus-induced arthritis in mice.
abstract: Staphylococcus aureus is one of the dominant pathogens that induce septic arthritis in immunocompromised hosts, e.g., patients suffering from rheumatoid arthritis treated with immunosuppressive drugs. S. aureus-induced arthritis leads to severe joint destruction and high mortality despite antibiotic treatment. Recently, interleukin-17A (IL-17A) has been discovered to be an important mediator of aseptic arthritis both in mice and humans, but its function in S. aureus-induced arthritis is largely unknown. Here, we investigated the role of IL-17A in host defense against arthritis following systemic and local S. aureus infection in vivo. IL-17A knockout mice and wild-type mice were inoculated systemically (intravenously) or locally (intra-articularly) with S. aureus. During systemic infection, IL-17A knockout mice lost significantly more weight than the wild-type mice did, but no differences were found in the mortality rate. The absence of IL-17A had no impact on clinical arthritis development but led to increased histopathological erosivity late during systemic S. aureus infection. Bacterial clearance in kidneys was increased in IL-17A knockout mice compared to the level in wild-type mice only 1 day after bacterial inoculation. During systemic S. aureus infection, serum IL-17F protein levels and mRNA levels in the lymph nodes were elevated in the IL-17A knockout mice compared to the level in wild-type mice. In contrast to systemic infection, the IL-17A knockout mice had increased synovitis and erosions and locally decreased clearance of bacteria 3 days after local bacterial inoculation. On the basis of these findings, we suggest that IL-17A is more important in local host defense than in systemic host defense against S. aureus-induced arthritis.
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, Box 480, SE 405 30 Göteborg, Sweden. louise.henningsson@rheuma.gu.se
authors.forename: Louise
authors.initials: L
authors.lastname: Henningsson
authors.forename: Pernilla
authors.initials: P
authors.lastname: Jirholt
authors.forename: Catharina
authors.initials: C
authors.lastname: Lindholm
authors.forename: Tove
authors.initials: T
authors.lastname: Eneljung
authors.forename: Elin
authors.initials: E
authors.lastname: Silverpil
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Anders
authors.initials: A
authors.lastname: Linden
authors.forename: Inger
authors.initials: I
authors.lastname: Gjertsson
mesh_terms: D000818:Animals; D001170:Arthritis, Infectious / Q000276:immunology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D007371:Interferon-gamma / Q000502:physiology; D020381:Interleukin-17 / Q000097:blood / Q000502:physiology*; D007668:Kidney / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus
chemical_list: C098680:Il17a protein, mouse; D020381:Interleukin-17; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma