Tumor necrosis factor receptor p55-deficient mice respond to acute Yersinia enterocolitica infection with less apoptosis and more effective host resistance.
Tumor necrosis factor (TNF) has generally been regarded as a protective cytokine in host defense against bacterial infections. In the present study, we evaluated the role of TNF in the acute phase of infection by Yersinia enterocolitica by using mice rendered genetically deficient in TNF receptor p55 (TNFRp55(-/-)). Unexpectedly, TNFRp55(-/-) mice showed more effective resistance to the bacteria, reflected in enhanced bacterial clearance and less tissue damage, than did control C57BL/6 mice. C57BL/6 mice showed evidence of extensive apoptosis in the spleen accompanied by a selective decrease in the CD4(+)-T-cell population of splenocytes, whereas TNFRp55(-/-) mice were spared these changes. The splenocytes from TNFRp55(-/-) mice also maintained a robust gamma interferon IFN-gamma response to mitogenic stimulation, while the comparable response in C57BL/6 mice was impaired. In addition, splenocytes harvested from infected mice demonstrated lower production of interleukin-10 IL-10 in TNFRp55(-/-) mice than in C57BL/6 mice. These findings suggest that Yersinia can induce TNFRp55-mediated apoptosis of splenocytes in the acute phase of the infection and that alteration of T-cell-generated cytokines can dramatically alter the early events in host defense against this pathogen.
Zhao
Y X
YX
Division of Rheumatology, Toronto Western Hospital, University of Toronto, Toronto, Canada.
Lajoie
G
G
Zhang
H
H
Chiu
B
B
Payne
U
U
Inman
R D
RD
D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis; D010586:Phagocytes / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D015009:Yersinia Infections / Q000276:immunology* / Q000473:pathology; D015008:Yersinia enterocolitica
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D016753:Interleukin-10; D009569:Nitric Oxide; D007371:Interferon-gamma