Department of Molecular Immunology, Institute of Industrial Science, University of Tokyo, Tokyo, Japan.
Nat Immunol. 2012 May 20;13(7):659-66. doi: 10.1038/ni.2307.
Although the mechanisms by which innate pathogen-recognition receptors enhance adaptive immune responses are increasingly well understood, whether signaling events from distinct classes of receptors affect each other in modulating adaptive immunity remains unclear. We found here that the activation of cytosolic RIG-I-like receptors (RLRs) resulted in the selective suppression of transcription of the gene encoding the p40 subunit of interleukin 12 (Il12b) that was effectively induced by the activation of Toll-like receptors (TLRs). The RLR-activated transcription factor IRF3 bound dominantly, relative to IRF5, to the Il12b promoter, where it interfered with the TLR-induced assembly of a productive transcription-factor complex. The activation of RLRs in mice attenuated TLR-induced responses of the T helper type 1 cell (T(H)1 cell) and interleukin 17-producing helper T cell (T(H)17 cell) subset types and, consequently, viral infection of mice caused death at sublethal doses of bacterial infection. The innate immune receptor cross-interference we describe may have implications for infection-associated clinical episodes.
尽管先天病原体识别受体增强适应性免疫反应的机制越来越被理解，但不同类别受体的信号事件是否会相互影响以调节适应性免疫仍然不清楚。我们在这里发现，胞质 RIG-I 样受体（RLR）的激活导致了白细胞介素 12（Il12b）p40 亚基基因转录的选择性抑制，而 Il12b 基因的转录是由 Toll 样受体（TLR）的激活有效诱导的。与 IRF5 相比，RLR 激活的转录因子 IRF3 主要结合到 Il12b 启动子上，在那里它干扰了 TLR 诱导的有效转录因子复合物的组装。RLR 在小鼠中的激活减弱了 TLR 诱导的 T 辅助细胞（T(H)1 细胞）和白细胞介素 17 产生辅助 T 细胞（T(H)17 细胞）亚群类型的反应，因此，在亚致死剂量的细菌感染下，病毒感染导致小鼠死亡。我们描述的先天免疫受体交叉干扰可能对感染相关的临床发作有影响。
