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Bacterial evasion of host immune defense: Yersinia enterocolitica encodes a suppressor for tumor necrosis factor
H U Beuscher1, F Rödel, A Forsberg
1Institute for Clinical Microbiology and Immunology, University of Erlangen/Nürnberg, Germany.
Abstract:
The ability of the enteropathogenic Yersinia enterocolitica to survive and proliferate in host tissue depends on a 70-kb plasmid known to encode a number of released Yersinia outer proteins that act as virulence factors by inducing cytotoxicity and inhibiting phagocytosis. This study demonstrates that one of the Yersinia outer proteins, the 41-kDa YopB, suppresses the production of tumor necrosis factor alpha (TNF-alpha), a macrophage-derived cytokine with central roles in the regulation 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 supernatant (CS+) of plasmid-bearing yersiniae, the effect which was blocked by anti-YopB antiserum. Second, suppression of TNF-alpha production, but not of interleukin-1 (IL-1) and IL-6, was induced by purified YopB. Third, in Yersinia-infected mice, no increase in TNF-alpha mRNA expression was observed in Peyer's patches, the primary site of bacterial invasion, compared with IL-1 (alpha and beta) mRNA. Finally, administration of anti-YopB antiserum to mice prior to infection with Y. enterocolitica increased TNF activity levels in Peyer's patches and coincided with a reduction in bacterial growth. The results thus provide direct evidence for a secreted eubacterial virulence factor that mediates selective 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 suppression of TNF-alpha production by YopB significantly contributes to the evasion of Y. enterocolitica from antibacterial host defense.
Insights
Yersinia enterocolitica uses the YopB protein to suppress tumor necrosis factor alpha (TNF-alpha) production, aiding bacterial evasion of immune defenses. This targeted cytokine suppression helps the pathogen survive within host tissues.
Area of Science:
- Microbiology
- Immunology
- Bacterial Pathogenesis
Background:
- Enteropathogenic Yersinia enterocolitica relies on a plasmid encoding virulence factors for host survival.
- Yersinia outer proteins (Yops) contribute to pathogenicity by inducing cytotoxicity and inhibiting phagocytosis.
Purpose of the Study:
- To investigate the role of Yersinia outer protein B (YopB) in modulating host immune responses, specifically the production of tumor necrosis factor alpha (TNF-alpha).
Main Methods:
- Macrophage cultures treated with Yersinia supernatant and purified YopB.
- Analysis of cytokine mRNA expression (TNF-alpha, IL-1, IL-6) in vitro and in vivo.
- Infection of mice with Y. enterocolitica, with and without anti-YopB antiserum administration.
Main Results:
- Yersinia supernatant and purified YopB suppressed TNF-alpha production in macrophages.
- YopB selectively inhibited TNF-alpha, not IL-1 or IL-6.
- In infected mice, YopB-mediated suppression of TNF-alpha was observed in Peyer's patches.
- Anti-YopB antiserum treatment reduced bacterial growth and increased TNF-alpha levels in vivo.
Conclusions:
- The Yersinia outer protein YopB is a secreted virulence factor that selectively suppresses TNF-alpha production.
- Suppression of TNF-alpha by YopB contributes significantly to Y. enterocolitica's evasion of host antibacterial defenses.