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

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.

• Authors: Margareta Verdrengh, James A Thomas, Olof H Hultgren
• Journal: Microbes and infection (Microbes Infect) Vol. 6 Issue 14 Pg. 1268-72 (Nov 2004) ISSN: 1286-4579 [Print] France
• PMID: 15555532 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• 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, metabolism)
• Receptors, Cell Surface (metabolism)
• Receptors, Interleukin (metabolism)
• Receptors, Interleukin-1 (genetics, metabolism)
• Receptors, Interleukin-18
• Signal Transduction
• Staphylococcal Infections (enzymology, immunology)
• Staphylococcus aureus (immunology)
• Survival Analysis
• Toll-Like Receptors