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

Microbes Infect. 2004 Nov;6(14):1268-72. doi: 10.1016/j.micinf.2004.08.009.

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 x 10(7) or 1 x 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 x 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteremia
  • Blood / microbiology
  • Body Weight
  • Colony Count, Microbial
  • Disease Susceptibility
  • Female
  • Immunity, Innate
  • Interleukin-1 / blood
  • Interleukin-1 Receptor-Associated Kinases
  • Interleukin-18 / blood
  • Interleukin-18 Receptor alpha Subunit
  • Kidney / microbiology
  • Male
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Receptors, Cell Surface / metabolism
  • Receptors, Interleukin / metabolism
  • Receptors, Interleukin-1 / genetics
  • Receptors, Interleukin-1 / metabolism
  • Receptors, Interleukin-18
  • Signal Transduction
  • Staphylococcal Infections / enzymology*
  • Staphylococcal Infections / immunology*
  • Staphylococcus aureus / immunology*
  • Survival Analysis
  • Toll-Like Receptors

Substances

  • Il18r1 protein, mouse
  • Interleukin-1
  • Interleukin-18
  • Interleukin-18 Receptor alpha Subunit
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Receptors, Interleukin
  • Receptors, Interleukin-1
  • Receptors, Interleukin-18
  • Toll-Like Receptors
  • Protein Kinases
  • Interleukin-1 Receptor-Associated Kinases