TUMOR-NECROSIS-FACTOR-ALPHA EXPRESSION INDUCED BY ANTI-YOPB ANTIBODIES COINCIDES WITH PROTECTION AGAINST YERSINIA-ENTEROCOLITICA INFECTION IN MICE

Previous studies have suggested that virulence of pathogenic Yersiniae is associated with a suppression of the local cytokine response. In t his context, the plasmid-encoded 41-kDa Yersinia outer protein B (YopB ) has been implicated with the lack of tumor necrosis factor-alpha (TN F-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 Yop B-induced suppression of TNF-alpha and bacterial survival in host tiss ue. Results are presented to show the ability of purified YopB to supp ress the release of TNF-alpha by macrophages, the effect of which was neutralized by monospecific anti-YopB antiserum. In mice orally infect ed with Y. enterocolitica, anti-YopB treatment on days 3 and 5 postinf ection, significantly decreased the recovery of live bacteria from PP. This observation correlated with a strong increase in TNF-alpha expre ssion, as determined by reverse transcription-polymerase chain reactio n and measuring the levels of TNF activity in homogenates of PP Moreov er, treatment of mice with a combination of anti-YopB and anti-TNF-alp ha antiserum, completely abrogated the beneficial effect of the anti-Y opB antiserum. In controls, expression of other proinflammatory cytoki nes such as interleukin-1 remained unaffected by either treatment. The refore, 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-al pha response in PP.