Kaisho Tsuneyasu, Akira Shizuo
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
Curr Mol Med. 2003 Jun;3(4):373-85. doi: 10.2174/1566524033479726.
Higher animals establish host defense by orchestrating innate and adaptive immunity. This is mediated by professional antigen presenting cells, i.e. dendritic cells (DCs). DCs can incorporate pathogens, produce a variety of cytokines, maturate, and present pathogen-derived peptides to T cells, thereby inducing T cell activation and differentiation. These responses are triggered by microbial recognition through type I transmembrane proteins, Toll-like receptors (TLRs) on DCs. TLRs consist of ten members and each TLR is involved in recognizing a variety of microorganism-derived molecular structures. TLR ligands include cell wall components, proteins, nucleic acids, and synthetic chemical compounds, all of which can activate DCs as immune adjuvants. Each TLR can activate DCs in a similar, but distinct manner. For example, TLRs can be divided into subgroups according to their type I interferon (IFN) inducing ability. TLR2 cannot induce IFN-alpha or IFN-beta, but TLR4 can lead to IFN-beta production. Meanwhile, TLR3, TLR7, and TLR9 can induce both IFN-alpha and IFN-beta. Recent evidences suggest that cytoplamic adapters for TLRs are especially crucial for this functional heterogeneity. Clarifying how DC function is regulated by TLRs should provide us with critical information for manipulating the host defense against a variety of diseases.
高等动物通过协调固有免疫和适应性免疫来建立宿主防御。这一过程由专职抗原呈递细胞介导，即树突状细胞（DCs）。DCs能够摄取病原体，产生多种细胞因子，成熟并将病原体衍生的肽呈递给T细胞，从而诱导T细胞活化和分化。这些反应是由DCs上的I型跨膜蛋白——Toll样受体（TLRs）对微生物的识别所触发的。TLRs由十个成员组成，每个TLR都参与识别多种微生物衍生的分子结构。TLR配体包括细胞壁成分、蛋白质、核酸和合成化合物，所有这些都可以作为免疫佐剂激活DCs。每个TLR都能以相似但又不同的方式激活DCs。例如，TLRs可根据其诱导I型干扰素（IFN）的能力分为亚组。TLR2不能诱导IFN-α或IFN-β，但TLR4可导致IFN-β的产生。同时，TLR3、TLR7和TLR9既能诱导IFN-α也能诱导IFN-β。最近的证据表明，TLRs的细胞质衔接蛋白对于这种功能异质性尤为关键。阐明TLRs如何调节DC功能将为我们提供操纵宿主防御各种疾病的关键信息。
