Toll‐like receptor interactions: tolerance of MyD88‐dependent cytokines but enhancement of MyD88‐independent interferon‐β production

Immunology - Tập 120 Số 1 - Trang 103-111 - 2007
Andrea Broad1, John A. Kirby1, David Jones1
1The Medical School, University of Newcastle, Newcastle-upon-Tyne, UK

Tóm tắt

SummaryToll‐like receptors (TLRs) signal through two main pathways: a myeloid differentiation factor (MyD)88‐dependent pathway that acts via nuclear factor κB (NF‐κB) to induce proinflammatory cytokines such as tumour necrosis factor‐α (TNF‐α) and a MyD88‐independent pathway that acts via type I interferons to increase the expression of interferon‐inducible genes. Repeated signalling through TLR4 and a number of other TLRs has been reported to result in a reduction in the subsequent proinflammatory cytokine response, a phenomenon known as TLR tolerance. In this study we have shown that, whilst NF‐κB activation and production of TNF‐α and interleukin‐12 by murine RAW264.7 and J774.2 cells in response to stimulation by TLR4, ‐5, ‐7 or ‐9, was reduced by prior stimulation with TLR4, ‐5, ‐7 or ‐9 ligands, the primary stimulation of TLR3, which does not use the MyD88 pathway, did not reduce the TNF‐α or interleukin‐12 responses to subsequent TLR stimulation. The response to TLR3 stimulation was not diminished by prior TLR ligand exposure. Furthermore, the production of interferon‐β (IFN‐β) following stimulation of TLR3 or ‐4, which is MyD88‐independent, was increased by prior activation of TLR4, ‐5, ‐7 or ‐9. In contrast, TLR9 ligand‐induced IFN‐β production, which is MyD88‐dependent, was tolerized by prior TLR stimulation. These results are consistent with differential regulation of MyD88‐dependent and MyD88‐independent cytokine production following serial activation of TLRs.

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Thông tin xuất bản

Immunology

Tập 120 Số 1

103-111

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