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 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.
Burdack
S
S
Institut für Klinische Mikrobiologie und Immunologie, Universität Erlangen/Nürnberg, Germany.
Schmidt
A
A
Knieschies
E
E
Röllinghoff
M
M
Beuscher
H U
HU
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology / Q000627:therapeutic use; D000918:Antibody Specificity; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D005260:Female; D007116:Immunization, Passive; D051379:Mice; D008807:Mice, Inbred BALB C; D010581:Peyer's Patches / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology; D015009:Yersinia Infections / Q000276:immunology* / Q000628:therapy; D015008:Yersinia enterocolitica / Q000276:immunology*
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; C078909:YopB protein, Yersinia