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 development of Yersinia-associated arthritis by evaluating the impact of tumor necrosis factor receptor p55 (TNFRp55) deficiency on Yersinia enterocolitica infection.


METHODS
TNFRp55-/- and C57BL/6 mice were inoculated intravenously with arthritogenic strain 8081 of Yenterocolitica serotype 0:8. Mice were observed daily for generating survival curves and monitoring arthritis. In subsequent sets of experiments, mice were sacrificed at day 14 after infection for examination of histopathology of joints, bacterial clearance, macrophage microbicidal activity, nitric oxide (NO) production, oxidative burst generation, and cytokine production.


RESULTS
There was an 80% mortality rate in TNFRp55-/- mice compared with 25% in the controls at 8 weeks after inoculation with 70 colony-forming units 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 the higher bacterial load in liver, spleen, and lungs, and with the increased levels of interleukin-10. TNFRp55-/- mice displayed impaired intracellular killing of bacteria by macrophages. This was associated with decreased NO production and impaired oxidative burst activity.


CONCLUSIONS
This study demonstrates that TNF signaling through TNFRp55 controls the severity of Yersinia-induced arthritis and implicates TNF-mediated macrophage microbicidal activity as a central event in this process.
Zhao
Y X
YX
The Toronto Hospital Arthritis Center and University of Toronto, Ontario, Canada.
Zhang
H
H
Chiu
B
B
Payne
U
U
Inman
R D
RD
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000917:Antibody Formation; D000918:Antibody Specificity; D015703:Antigens, CD / Q000627:therapeutic use*; D001170:Arthritis, Infectious / Q000517:prevention & control*; D001402:B-Lymphocytes / Q000382:microbiology; D001770:Blood Bactericidal Activity; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000382:microbiology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000378:metabolism; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D047888:Receptors, Tumor Necrosis Factor, Type I; D016897:Respiratory Burst; D012720:Severity of Illness Index; D015009:Yersinia Infections; D015008:Yersinia enterocolitica
D000888:Antibodies, Anti-Idiotypic; D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; C049937:anti-IgA; C044203:anti-IgM; D016753:Interleukin-10; D009569:Nitric Oxide; D007371:Interferon-gamma