黏膜上皮细胞:病毒侵染与机体免疫的初始交汇处  

Mucosal epithelial cell: the initial convergence of viral infection and host immunity

作　　者：鄢慧民[1] 

机构地区：[1]中国科学院武汉病毒研究所,病毒学国家重点实验室黏膜免疫学科组,武汉430071

出　　处：《生命科学》2016年第2期248-257,共10页Chinese Bulletin of Life Sciences

基　　金：国家自然科学基金项目(30471584;30670097;31270207)

摘　　要：黏膜上皮细胞构成了包括呼吸道、消化道、泌尿生殖道在内的一个广阔的黏膜界面。黏膜上皮细胞、免疫细胞、免疫分子共同组成黏膜相关淋巴组织,构成了一个完整的黏膜免疫防御系统。黏膜上皮细胞通常是病毒感染的初始靶细胞。大多数DNA和RNA病毒都能直接感染黏膜上皮细胞。黏膜上皮细胞在病毒复制过程中可通过各种模式识别受体感应病毒的病原相关分子模式,从而识别病毒,并启动抗病毒固有免疫应答。近10年来,巨噬细胞炎症小体和caspase-1信号通路激活及其相应的抗感染效应成为固有免疫研究一个热点。病原相关分子模式被巨噬细胞识别,启动形成不同类型的炎症小体,激活caspase-1信号通路,诱导炎性细胞因子IL-1β和IL-18产生,造成细胞焦亡。对巨噬细胞炎症小体的研究,加深了人们对固有免疫的理解,促进了免疫识别、免疫信号转导、免疫应答、免疫调节、免疫病理等各个方面的研究。与固有免疫细胞一样,黏膜上皮细胞具有自身特征性的模式识别受体表达和分布。黏膜上皮细胞通过模式识别受体识别病毒病原相关分子模式,并激活NF-κB信号通路,产生炎性细胞因子、I型和III型干扰素,实现快速的炎性应答和发挥抗病毒作用。黏膜上皮细胞的这种快速应答释放出的各类细胞因子共同招募、激活和协调固有免疫细胞发挥固有免疫应答,并进一步调节、诱导特异性免疫细胞产生特异性抗体和T细胞应答。可见,黏膜上皮细胞是病毒侵染与机体免疫的一个最初的重要交汇处。在这个初始交汇处,黏膜上皮细胞不仅对局部黏膜免疫应答起作用,而且对系统免疫应答起着决定性调节作用。然而,黏膜上皮细胞对病原相关分子模式的识别以及相关炎症通路的激活尚处于启蒙时期。黏膜上皮细胞与炎症小体的关系值得进一步研究。新发现的III型干扰素及其�Mucosal epithelial cell composes a large mucosal physical interface in respiratory, gastrointestinal and genital tracts. Together with different immune cells and molecules, the mucosal epithelial cell comprises a so called mucosa-associated lymphoid tissue, which functions as a whole mucosal immune system to defend infection. The mucosal epithelial cell is usually the very initial target cell and is readily infected by a wide variety of DNA and RNA viruses. During viral replication, the mucosal epithelial cell can sense pathogen-associated molecular patterns（PAMPs） of virus with a diverse range of pattern recognition receptors（PRRs）, and detect virus infection to initiate innate immune response. In recent decade, inflammsome and caspase-1 pathway were investigated intensively in macrophage and attracted a lot of attention. Usually, inflammasome as a multi-protein molecular scaffold can be induced in macrophage after intracellular recognition of PAMPs. Then activation of inflammatory caspase-1 and the processing of proinflammatory cytokines of the IL-1 family may result in pyroptosis. This knowledge has been integrated into further study on innate immune recognition and signaling, immune response and regulation, as well as in immune pathology. Similar with immune cells, different mucosal epithelial cell expresses different combination of PRRs, which can recognize viral PAMPs and activate NF-κB pathway to produce proinflammatory cytokines, type I and III interferons for antiviral defense. Furthermore, the cytokines communicate with intraepithelial innate immune cells such as dendritic cells, NK cells and regulate specific antibody and T cell responses. Therefore, mucosal epithelial cell is an initial convergence of viral infection and host immunity, in which the mucosal epithelial cell not only plays roles in local defense against viral infection, but also plays diverse and multifaceted regulatory roles in systemic immune response. However, the study on the PAMPs recognition of the mucosal epithelial cell

关 键 词：黏膜上皮细胞 病毒感染 模式识别受体 病原相关分子模式 固有免疫应答 干扰素 黏膜免疫应答 Ig A抗体 抗病毒机制 

分 类 号：Q813.11[生物学—生物工程]