| Abstrakt: |
A murine model of acute hematogenous osteomyelitis was used to study the immune response following Staphylococcus aureusinfection 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. Lymphnode 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 (Vβ2, Vβ3, Vβ9, and Vβ10) 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 (Vβ11, Vβ12, Vβ13, Vβ14, and Vβ16) 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 Vβ14 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‐γ showed a late and relatively short activation pattern compared with the inflammatory cytokines interleukin‐1, interleukin‐6, and tumor necrosis factor‐α. The results suggest that Staphylococcus aureusbone 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. |
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