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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bacteremia
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Blood / microbiology
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Body Weight
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Colony Count, Microbial
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Disease Susceptibility
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Female
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Immunity, Innate
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Interleukin-1 / blood
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Interleukin-1 Receptor-Associated Kinases
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Interleukin-18 / blood
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Interleukin-18 Receptor alpha Subunit
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Kidney / microbiology
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Male
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Membrane Glycoproteins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Protein Kinases / genetics
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Protein Kinases / metabolism*
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Receptors, Cell Surface / metabolism
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Receptors, Interleukin / metabolism
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Receptors, Interleukin-1 / genetics
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Receptors, Interleukin-1 / metabolism
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Receptors, Interleukin-18
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Signal Transduction
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Staphylococcal Infections / enzymology*
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Staphylococcal Infections / immunology*
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Staphylococcus aureus / immunology*
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Survival Analysis
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Toll-Like Receptors
Substances
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Il18r1 protein, mouse
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Interleukin-1
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Interleukin-18
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Interleukin-18 Receptor alpha Subunit
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Membrane Glycoproteins
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Receptors, Cell Surface
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Receptors, Interleukin
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Receptors, Interleukin-1
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Receptors, Interleukin-18
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Toll-Like Receptors
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Protein Kinases
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Interleukin-1 Receptor-Associated Kinases