Abstract
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.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Bone Marrow Transplantation
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Dermatitis, Contact / immunology*
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Dermatitis, Contact / metabolism
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Interleukin-1 / immunology
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Interleukin-1 / metabolism
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Interleukin-18 / immunology
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Interleukin-18 / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Myeloid Differentiation Factor 88 / genetics
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Myeloid Differentiation Factor 88 / immunology*
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Myeloid Differentiation Factor 88 / metabolism
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Receptors, Interleukin-1 / genetics
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Receptors, Interleukin-1 / immunology*
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Receptors, Interleukin-1 / metabolism
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Receptors, Interleukin-18 / genetics
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Receptors, Interleukin-18 / immunology*
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Receptors, Interleukin-18 / metabolism
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Signal Transduction / immunology*
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Toll-Like Receptor 2 / genetics
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Toll-Like Receptor 4 / genetics
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Toll-Like Receptor 6 / genetics
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Toll-Like Receptor 9 / genetics
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Transplantation Chimera
Substances
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Interleukin-1
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Interleukin-18
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Myd88 protein, mouse
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Myeloid Differentiation Factor 88
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Receptors, Interleukin-1
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Receptors, Interleukin-18
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Tlr2 protein, mouse
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Tlr4 protein, mouse
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Tlr6 protein, mouse
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Tlr9 protein, mouse
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Toll-Like Receptor 2
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Toll-Like Receptor 4
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Toll-Like Receptor 6
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Toll-Like Receptor 9