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Infect. Immun., 04 1995, 1270-1277, Vol 63, No. 4
HU Beuscher, F Rodel, A Forsberg and M Rollinghoff
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.
Copyright © 1995, American Society for Microbiology
Bacterial evasion of host immune defense: Yersinia enterocolitica encodes a suppressor for tumor necrosis factor alpha expression
Institute for Clinical Microbiology and Immunology, University of Erlangen/Nurnberg, Germany.
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