The impact of tacrolimus on the immunopathogenesis of staphylococcal enterotoxin-induced systemic inflammatory response syndrome and pneumonia

Ashenafi Y. Tilahun, Melissa J. Karau, Chad R. Clark, Robin Patel, Govindarajan Rajagopalan

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Staphylococcal superantigens (SAg) are a family of potent exotoxins produced by Staphylococcus aureus. They play an important role in the pathogenesis of staphylococcal shock and pneumonia by causing a robust activation of the immune system and eliciting a strong surge in systemic cytokine and chemokine levels. Given the biological functions of SAg, we evaluated the efficacy of tacrolimus, a potent immunosuppressive agent, in the prophylaxis and therapy of staphylococcal TSS and pneumonia using human leukocyte antigen (HLA)-DR3 transgenic mice. Tacrolimus significantly inhibited staphylococcal SAg induced T cell activation in vitro. In vivo, tacrolimus significantly suppressed the SAg-induced elevation in serum cytokine and chemokine levels when given prophylactically, when administered immediately or even 2 h following systemic SAg challenge. Paradoxically, neither the prophylactic nor post-exposure treatment with tacrolimus protected mice from lethal SAg-induced TSS. A closer examination revealed that tacrolimus failed to suppress SAg-induced T cell proliferation and systemic pathology, including gut dysfunction. Tacrolimus also failed to protect from lethal pneumonia induced by a SAg-producing S. aureus strain. Thus, our study showed that even though T cell activation by SAg plays a major role in the immunopathogenesis of TSS and pneumonia, tacrolimus alone has no beneficial effect.

Original languageEnglish (US)
Pages (from-to)528-536
Number of pages9
JournalMicrobes and Infection
Volume14
Issue number6
DOIs
StatePublished - Jun 1 2012

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Keywords

  • Chemokines
  • Cytokines
  • HLA class II transgenic mice
  • Rodents
  • T lymphocytes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases

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