Bacterial cytokine antagonists encoded by pathogenic yersiniae

Proinflammatory cytokines such as tumor necrosis factor alpha (TNF alpha) are important immunoregulatory mediators of the antibacterial host defense. Previous studies have suggested that virulence of pathogenic Yersiniae is associated with suppression of the local cytokine response. In this context, the plasmid-encoded 41 kDa Yersinia outer protein B (YopB) has been implicated with a lack of 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. 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 RT-PCR 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 IL-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.