Suppression of cytokines in mice by protein A-V antigen fusion peptide and restoration of synthesis by active immunization

R. Nakajima, V. L. Motin, R. R. Brubaker

Research output: Contribution to journalArticle

161 Scopus citations

Abstract

It is established that an ~70-kb Lcr plasmid enables Yersinia pestis, the causative agent of bubonic plague, to multiply in focal necrotic lesions within visceral organs of mice by preventing net synthesis of the cytokines tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ), thereby minimizing inflammation (Lcr+). Rabbit antiserum raised against cloned staphylococcal protein A-V antigen fusion peptide (PAV) is known to passively immunize mice against 10 minimum lethal doses of intravenously injected Lcr+ cells of Y. pestis. In this study, injected PAV suppressed TNF-α and IFN-γ in mice challenged with avirulent V antigen-deficient Y. pestis (lcrV or Lcr-) and promoted survival in vivo of these isolates as well as salmonellae and Listeria monocytogenes (with which the outcome was lethal). Active immunization of mice with PAV protected against 1,000 minimum lethal doses of intravenously injected Lcr+ cells of Y. pestis and Yersinia pseudotuberculosis but not Yersinia enterocolitica. The progressive necrosis provoked by Lcr+ cells of Y. pestis in visceral organs of nonimmunized mice was replaced after active immunization with PAV by massive infiltration of neutrophils and mononuclear cells (which generated protective granulomas indistinguishable from those formed against avirulent Ler- mutants in nonimmunized mice). Distinct multiple abscesses typical of Lcr+ cells of Y. pseudotuberculosis were prevented by similar immunization. Significant synthesis of TNF-α and IFN-γ occurred in spleens of mice actively immunized with PAV after challenge with Lcr+ cells of Y. pestis. These findings suggest that V antigen contributes to disease by suppressing the normal inflammatory response.

Original languageEnglish (US)
Pages (from-to)3021-3029
Number of pages9
JournalInfection and immunity
Volume63
Issue number8
DOIs
StatePublished - 1995

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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