Tumor necrosis factor receptor p55 controls the severity of arthritis in experimental Yersinia enterocolitica infection

Objective. To dissect the host defense mechanisms in relation to the develo pment of Yersinia-associated arthritis by evaluating the impact of tumor ne crosis factor receptor p55 (TNFRp55) deficiency on Yersinia enterocolitica infection. Methods, TNFRp55-/- and C57BL/6 mice were inoculated intravenously with art hritogenic strain 8081 of Y enterocolitica serotype 0:8, Mice were observed daily for generating survival curves and monitoring arthritis. In subseque nt sets of experiments, mice were sacrificed at day 14 after infection for examination of histopathology of joints, bacterial clearance, macrophage mi crobicidal activity, nitric oxide (NO) production, oxidative burst generati on, and cytokine production, Results. There was an 80% mortality rate in TNFRp55-/- mice compared with 2 5% in the controls at 8 weeks after inoculation with 70 colony-forming unit s of Y enterocolitica 0:8, Histologic examination of joint tissues revealed that TNFRp55-/- mice developed more severe arthritis, including cartilage degradation and bony destruction, than controls at day 14 after infection, The more extensive joint pathology in TNFRp55-/- mice was correlated with t he higher bacterial load in liver, spleen, and lungs, and with the increase d levels of interleukin-10. TNFRp55-/- mice displayed impaired intracellula r killing of bacteria by macrophages. This was associated with decreased NO production and impaired oxidative burst activity. Conclusion. This study demonstrates that TNF signaling through TNFRp55 cont rols the severity of Yersinia-induced arthritis and implicates TNF-mediated macrophage microbicidal activity as a central event in this process.