title: 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.affiliation: Department of Rheumatology and Inflammation Research, Göteborg University, Guldhedsgatan 10 A, S-413 46 Göteborg, Sweden. margareta.verdrengh@rheuma.gu.se
authors.forename: Margareta
authors.initials: M
authors.lastname: Verdrengh
authors.forename: James A
authors.initials: JA
authors.lastname: Thomas
authors.forename: Olof H
authors.initials: OH
authors.lastname: Hultgren
mesh_terms: D000818:Animals; D016470:Bacteremia; D001769:Blood / Q000382:microbiology; D001835:Body Weight; D015169:Colony Count, Microbial; D004198:Disease Susceptibility; D005260:Female; D007113:Immunity, Innate; D007375:Interleukin-1 / Q000097:blood; D053592:Interleukin-1 Receptor-Associated Kinases; D020382:Interleukin-18 / Q000097:blood; D053727:Interleukin-18 Receptor alpha Subunit; D007668:Kidney / Q000382:microbiology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism; D053724:Receptors, Interleukin-18; D015398:Signal Transduction; D013203:Staphylococcal Infections / Q000201:enzymology* / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D016019:Survival Analysis; D051193:Toll-Like Receptors
chemical_list: C508573:Il18r1 protein, mouse; D007375:Interleukin-1; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1; D053724:Receptors, Interleukin-18; D051193:Toll-Like Receptors; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases