IL-1 receptor-associated kinase 1 mediates protection against Staphylococcus aureus infection

Margareta Verdrengh, James A. Thomas, Olof H. Hultgren

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

The interleukin-1 receptor-associated kinase-1 (IRAK-1) mediates signal transduction from Toll-like/IL-1/IL-18 receptors. Though a critical protective role against Staphylococcus aureus infection has been previously attributed to myeloid differentiation factor 88 (MyD88) and IRAK-4, both also involved in TLR/IL-1/IL-18 signaling, the role of IRAK-1 is unknown. IRAK-1-deficient (IRAK-1 -/-) and wild-type mice were inoculated i.v. with 2 × 10 7 or 1 × 10 6 S. aureus per mouse to evaluate the role of IRAK-1 in S. aureus sepsis. Since IRAK-1 transduces IL-1R signals, IL-1R -/- mice were also included in experiments. IRAK-1 -/- mice are susceptible to a high dose of S. aureus compared to wild-type controls. In contrast to the high mortality and extensive weight loss seen in IL-1R-deficient mice in response to 1 × 10 6 S. aureus, IRAK-1 -/- mice are resistant to this low dose of S. aureus. Thus IRAK-1 plays an important role in the host response to staphylococcal sepsis.

Original languageEnglish (US)
Pages (from-to)1268-1272
Number of pages5
JournalMicrobes and Infection
Volume6
Issue number14
DOIs
StatePublished - Nov 2004

Keywords

  • Bacterial
  • Cytokine receptors
  • Inflammation
  • Signal transduction
  • Transgenic/knockout

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases

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