Division of Immunology, Faculty of Chemistry, Biochemistry and Pharmacy, National University of San Luis, Laboratory of Immunopathology, Multidisciplinary Institute of Biological Investigations - San Luis, CONICET, San Luis, Argentina.
Int Immunopharmacol. 2011 Oct;11(10):1457-63. doi: 10.1016/j.intimp.2011.05.002. Epub 2011 May 18.
Innate immune cells have evolved to sense microbial pathogens through pattern recognition receptors (PRRs), which interact with conserved pathogen-associated molecular patterns (PAMPs) to convey microbial information into immune cell signaling and activation events. PRRs also recognize endogenous damage-associated molecular patterns (DAMPs), including alarmins released during microbial invasion, initiation of autoimmune inflammation or tumor growth. In spite of the well-established role of Toll-like receptors (TLRs) in mediating these recognition events, compelling evidence supports a central function for lectin-glycan interactions in promoting microbial sensing and evoking immune responses. Here we discuss the role of glycans and lectins (particularly galectins) in mediating microbial recognition and initiation of innate immune responses. Both microbes and host cells are sources of glycan-containing information which is, at least in part, decoded by endogenous glycan-binding proteins or lectins, including C-type lectins, siglecs and galectins. Although C-type lectins and siglecs can recognize microbial glycans when expressed on the cell surface of innate immune cells, galectins mainly function as soluble mediators that bridge microbial or host glycans to amplify or attenuate immune responses. Galectins are widely expressed in host cells and play important roles during different steps of infection such as pathogen recognition, invasion and resolution. In addition, recent studies report the presence of conserved 'galectin-like' domains in certain pathogens including helminths and protistan parasites, suggesting that they could also serve as potential virulence factors that influence the outcome and course of infection. Understanding the role of lectin-glycan interactions and the relevance of PRR or PAMP glycosylation in microbial recognition might contribute to the design of novel prophylactic and therapeutic strategies.
天然免疫细胞通过模式识别受体 (PRRs) 进化而来，以识别微生物病原体，这些受体与保守的病原体相关分子模式 (PAMPs) 相互作用，将微生物信息传递到免疫细胞信号和激活事件中。PRRs 还识别内源性损伤相关分子模式 (DAMPs)，包括在微生物入侵、自身免疫炎症或肿瘤生长开始时释放的警报素。尽管 Toll 样受体 (TLRs) 在介导这些识别事件中发挥了作用，但令人信服的证据支持凝集素-糖相互作用在促进微生物感应和引发免疫反应中的核心作用。在这里，我们讨论糖和凝集素（特别是半乳糖凝集素）在介导微生物识别和启动先天免疫反应中的作用。微生物和宿主细胞都是糖含量信息的来源，这些信息至少部分由内源性糖结合蛋白或凝集素（包括 C 型凝集素、siglecs 和半乳糖凝集素）解码。尽管 C 型凝集素和 siglecs 在先天免疫细胞的细胞表面表达时可以识别微生物糖，但半乳糖凝集素主要作为可溶性介质发挥作用，可桥接微生物或宿主糖，从而放大或减弱免疫反应。半乳糖凝集素广泛表达于宿主细胞中，并在感染的不同阶段（如病原体识别、入侵和解决）发挥重要作用。此外，最近的研究报告称，某些病原体（包括蠕虫和原生动物寄生虫）中存在保守的“半乳糖凝集素样”结构域，这表明它们也可能作为潜在的毒力因子，影响感染的结果和进程。了解凝集素-糖相互作用的作用以及 PRR 或 PAMP 糖基化在微生物识别中的相关性可能有助于设计新的预防和治疗策略。
