201203固有免疫研究进展.ppt

* Fig. 2. TLR7 and TLR9 signaling pathway. TLR7 and TLR9 recruit MyD88 to induce type I IFN and inflammatory responses through the activation of IRF7 and NF-kB, respectively. In pDC, MyD88 form a signaling complex with IRAK1, IRAK4, IKKa, TRAF3, TRAF6, OPN-i and IRF7. In response to ligand stimulation, IRF7 is phosphorylated by IRAK1 and IKKa, and translocates to the nuclei to regulate expression of type I IFN genes, especially IFNa. TRAF3, IRAK1, IKKa and OPN-i are indispensable for IRF7 activation and dispensable for NF-kB activation, however, IRAK4 and TRAF6 are indispensable for both NF-kB and IRF7 activation. Fig. 1. Putative RIG-I ligands. RIG-I has been reported to be triggered experimentally by a variety of RNA agonists. 5′-PPP–bearing RNAs are shown in green, RNAs without 5′-PPPs in blue, and RNAs that may have different 5′-end characteristics in orange. An antagonist is shown in black. Activated RIG-I promotes the induction of interferons and other pro-inflammatory cytokines via the mitochondrial adaptor MAVS (bold red arrows). MAVS-dependent induction of pro-interleukin-1b allows it to be processed into mature interleukin-1b by the inflammasome, which can be directly activated by RIG-I in a MAVS-independent manner. SCIENCE,2010;327:284 * * Fig. 1. Differential roles of retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) in RNA virus recognition. RIG-I recognizes 5￠-triphosphate RNA and short dsRNA, whereas MDA5 discriminates long dsRNA generated during the course of virus infection. RNA viruses are differentially recognized by RIG-I and MDA5. RIG-I is responsible for detecting Paramyxoviridae, Orthomyxoviridae, Rhabdoviridae, and some Flaviviridae family members. By contrast, MDA5 recognizes Picornaviridae family members. Some viruses such as West Nile virus and reovirus are detected by both RIG-I and MDA5. Laboratory of genetics and physiology-2 (LGP2) is reported to be a genitive regulator for the RIG-I and MDA5