BACTERIAL EVASION OF HOST IMMUNE DEFENSE - YERSINIA-ENTEROCOLITICA ENCODES A SUPPRESSOR FOR TUMOR-NECROSIS-FACTOR-ALPHA EXPRESSION

The ability of the enteropathogenic Yersinia enterocolitica to survive and proliferate in host tissue depends on a 70-kb plasmid known to en code a number of released Yersinia outer proteins that act as virulenc e factors by inducing cytotoxicity and inhibiting phagocytosis, This s tudy demonstrates that one of the Yersinia outer proteins; the 41-kDa YopB, suppresses the production of tumor necrosis factor alpha (TNP-al pha), a macrophage-derived cytokine with central roles in the regulati on of immune and inflammatory responses to infection, This conclusion is based on several lines of evidence, First, in macrophage cultures, suppression of TNF-alpha mRNA expression was induced by culture supern atant (CS+) of plasmid-bearing yersiniae, the effect which was blocked by anti-YopB antiserum. Second, suppression of TNF-alpha production, but not of interleukin-l (IL-1) and IL-6, was induced by purified YopB , Third, in Yersinia-infected mice, no increase in TNF-alpha mRNA expr ession was observed in Peyer's patches, the primary site of bacterial invasion, compared with IL-1 (alpha and beta) mRNA, Finally, administr ation of anti-YopB antiserum to mice prior to infection with Y. Entero colitica increased TNF activity levels in Peyer's patches and coincide d with a reduction in bacterial growth. The results thus provide direc t evidence for a secreted eubacterial virulence factor that mediates s elective suppression of TNF-alpha production, Although suppression of this single cytokine response is probably not sufficient to facilitate survival of the infecting organisms, the results suggest that suppres sion of TNF-ru production by YopB significantly contributes to tile ev asion of Y. enterocolitica from antibacterial host defense,