title: Experimental acute hematogenous osteomyelitis in mice. II. Influence of Staphylococcus aureus infection on T-cell immunity.
abstract: A murine model of acute hematogenous osteomyelitis was used to study the immune response following Staphylococcus aureus infection and to examine the hypothesis that the bacteria may modify T-cell responses due to the production of bacterial enterotoxins with mitogenic or superantigenic activity. Lymph-node T cell-receptor expression was assessed with use of flow cytometry and reverse transcription-polymerase chain reaction techniques, and increased apoptosis (programmed cell death) in T-cell subsets was monitored. The expression and levels of circulating cytokines and T-cell cytokines within tissues surrounding the damaged area of the proximal tibia were also investigated. Analysis of T-cell receptors in experimental osteomyelitis revealed two distinct patterns of T-cell evolution during the disease. Certain T-cell subsets (Vbeta2, Vbeta3, Vbeta9, and Vbeta10) were activated and expanded during the first 24 hours after infection; they reached maximum levels 6 days after infection, followed by a return to pre-infection levels. In contrast, other T-cell subsets (Vbeta11, Vbeta12, Vbeta13, Vbeta14, and Vbeta16) contracted during the first 24 hours after infection, followed by expansion to a maximum level 9 days after infection. Activation and proliferation of T-cell subsets (notably Vbeta14 T cells) was followed by apoptosis, suggesting that staphylococcal bone infection caused superantigenic-like effects on the mouse immune system. Analysis of cytokine responses in local tissue revealed that the T-cell cytokines interleukin-2 and interferon-gamma showed a late and relatively short activation pattern compared with the inflammatory cytokines interleukin-1, interleukin-6, and tumor necrosis factor-alpha. The results suggest that Staphylococcus aureus bone infection may undermine the antibacterial immune response through downregulation of T-cell immunity and immune-cytokine production, which could increase the severity of the systemic infection and local osseous destruction that occur with acute hematogenous osteomyelitis.
authors.affiliation: Department of Orthopaedic Surgery, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
authors.forename: K S
authors.initials: KS
authors.lastname: Yoon
authors.forename: R H
authors.initials: RH
authors.lastname: Fitzgerald
authors.forename: S
authors.initials: S
authors.lastname: Sud
authors.forename: Z
authors.initials: Z
authors.lastname: Song
authors.forename: P H
authors.initials: PH
authors.lastname: Wooley
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016207:Cytokines / Q000097:blood / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D007109:Immunity / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D010019:Osteomyelitis / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D013203:Staphylococcal Infections / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*; D013977:Tibia / Q000503:physiopathology
chemical_list: D016207:Cytokines