Contrasting roles of the IL-1 and IL-18 receptors in MyD88-dependent contact hypersensitivity.
Contact hypersensitivity (CHS) requires activation of the innate immune system, and results in an adaptive immune response. Many cells of the innate immune system use Toll-like receptors (TLRs), which signal through the adaptor protein, MyD88, to initiate an immune response. MyD88 is also required for signaling downstream of the IL-1 and Il-18 receptors (IL-1R and IL-18R, respectively). Herein, we studied the MyD88 signaling pathway in the CHS response to DNFB. Mice deficient in MyD88 were unable to mount a CHS response to DNFB. In contrast, mice deficient in Toll/IL-1R-containing adaptor-inducing IFN-beta, TLR2, TLR4, TLR6, and TLR9 had no defect in their ability to respond to DNFB. Although both IL-1R and IL-18R-deficient mice showed a reduced CHS response to DNFB, in bone marrow chimera and adoptive transfer experiments, we found that MyD88 and the IL-18R were required in a radioresistant cell in the sensitization phase of the CHS response. In contrast, similar strategies revealed that the IL-1R was required in a radiosensitive cell in the sensitization phase of the CHS response. Taken together, these data indicate that the IL-1R and IL-18R/MyD88 pathways are required in distinctly different cells during the sensitization phase of CHS.
Klekotka
Paul A
PA
Division of Dermatology, Department of Medicine, St Louis, Missouri, USA.
Yang
Liping
L
Yokoyama
Wayne M
WM
D019264:Adoptive Transfer; D000818:Animals; D016026:Bone Marrow Transplantation; D003877:Dermatitis, Contact / Q000276:immunology* / Q000378:metabolism; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism; D020382:Interleukin-18 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D053724:Receptors, Interleukin-18 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D051216:Toll-Like Receptor 6 / Q000235:genetics; D051217:Toll-Like Receptor 9 / Q000235:genetics; D018183:Transplantation Chimera
D007375:Interleukin-1; D020382:Interleukin-18; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D017472:Receptors, Interleukin-1; D053724:Receptors, Interleukin-18; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; C495369:Tlr6 protein, mouse; C495370:Tlr9 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D051217:Toll-Like Receptor 9