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 cyt okine in host defense against bacterial infections. In the present study, w e evaluated the role of TNF in the acute phase of infection by Yersinia ent erocolitica by using mice rendered genetically deficient in TNF receptor p5 5 (TNFRp55(-/-)). Unexpectedly, TNFRp55(-/-) mice showed more effective res istance 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 i n the CD4(+)-T-cell population of splenocytes, whereas TNFRp55(-/-) mice we re spared these changes. The splenocytes from TNFRp55(-/-) mice also mainta ined a robust gamma interferon IFN-gamma response to mitogenic stimulation, while the comparable response in C57BL/6 mice was impaired. In addition, s plenocytes harvested from infected mice demonstrated lower production of in terleukin-10 IL-10 in TNFRp55(-/-) mice than in C57BL/6 mice. These finding s suggest that Yersinia can induce TNFRp55-mediated apoptosis of splenocyte s in the acute phase of the infection and that alteration of T-cell-generat ed cytokines can dramatically alter the early events in host defense agains t this pathogen.