Tumor necrosis factor-alpha expression induced by anti-YopB antibodies coincides with protection against Yersinia enterocolitica infection in mice.

Abstract

Previous studies have suggested that virulence of pathogenic Yersiniae is associated with a suppression of the local cytokine response. In this context, the plasmid-encoded 41-kDa Yersinia outer protein B (YopB) has been implicated with the lack of tumor necrosis factor-alpha (TNF-alpha) expression in Peyer's patches (PP), following oral infection of mice with the enteropathogenic Yersinia enterocolitica. The present study was performed to further evaluate the relationships between YopB-induced suppression of TNF-alpha and bacterial survival in host tissue. Results are presented to show the ability of purified YopB to suppress the release of TNF-alpha by macrophages, the effect of which was neutralized by monospecific anti-YopB antiserum. In mice orally infected with Y. enterocolitica, anti-YopB treatment on days 3 and 5 postinfection, significantly decreased the recovery of live bacteria from PP. This observation correlated with a strong increase in TNF-alpha expression, as determined by reverse transcription-polymerase chain reaction and measuring the levels of TNF activity in homogenates of PP. Moreover, treatment of mice with a combination of anti-YopB and anti-TNF-alpha antiserum, completely abrogated the beneficial effect of the anti-YopB antiserum. In controls, expression of other proinflammatory cytokines such as interleukin-1 remained unaffected by either treatment. Therefore, the results indicate that endogenous TNF-alpha is required for eradication of Y. enterocolitica from host tissue, and further imply that YopB significantly contributes to suppression of the local TNF-alpha response in PP.