Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3–mediated pathway
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- Sudan He
- Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, Suzhou 215123, China; and
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- Yuqiong Liang
- National Institute of Biological Sciences, Beijing 102206, China
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- Feng Shao
- National Institute of Biological Sciences, Beijing 102206, China
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- Xiaodong Wang
- National Institute of Biological Sciences, Beijing 102206, China
抄録
<jats:p>We report here that mouse macrophages undergo receptor-interacting kinase-3 (RIP3)-dependent but TNF-α–independent necrosis when Toll-like receptors (TLR) 3 and 4 are activated by poly(I:C) and LPS, respectively. An adaptor protein, Toll/IL-1 receptor domain-containing adapter inducing IFN-β (TRIF/TICAM-1), which is dispensable for TNF-α–induced necrosis, forms a complex with RIP3 upon TLR3/TLR4 activation and is essential for TLR3/TLR4-induced necrosis. Mice without RIP3 or functional TRIF did not show macrophage loss and elevation of inflammatory cytokines when they were exposed to LPS. Necrosis in mouse macrophages induced by either TNFR or TLR3/TLR4 is executed by reactive oxygen species. Taken together, these data indicate that there are multiple upstream necrosis-initiating signaling pathways converging on the RIP3 during an innate immune response to viral and bacterial infections in mammals.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 108 (50), 20054-20059, 2011-11-28
Proceedings of the National Academy of Sciences