Willment Janet A
Medical Research Council Centre for Medical Mycology, University of Exeter, Exeter, UK.
Mol Microbiol. 2022 Mar;117(3):632-660. doi: 10.1111/mmi.14837. Epub 2021 Dec 6.
The use of soluble fusion proteins of pattern recognition receptors (PRRs) used in the detection of exogenous and endogenous ligands has helped resolve the roles of PRRs in the innate immune response to pathogens, how they shape the adaptive immune response, and function in maintaining homeostasis. Using the immunoglobulin (Ig) crystallizable fragment (Fc) domain as a fusion partner, the PRR fusion proteins are soluble, stable, easily purified, have increased affinity due to the Fc homodimerization properties, and consequently have been used in a wide range of applications such as flow cytometry, screening of protein and glycan arrays, and immunofluorescent microscopy. This review will predominantly focus on the recognition of pathogens by the cell membrane-expressed glycan-binding proteins of the C-type lectin receptor (CLR) subgroup of PRRs. PRRs bind to conserved pathogen-associated molecular patterns (PAMPs), such as glycans, usually located within or on the outer surface of the pathogen. Significantly, many glycans structures are identical on both host and pathogen (e.g. the Lewis (Le) X glycan), allowing the use of Fc CLR fusion proteins with known endogenous and/or exogenous ligands as tools to identify pathogen structures that are able to interact with the immune system. Screens of highly purified pathogen-derived cell wall components have enabled identification of many unique PAMP structures recognized by CLRs. This review highlights studies using Fc CLR fusion proteins, with emphasis on the PAMPs found in fungi, bacteria, viruses, and parasites. The structure and unique features of the different CLR families is presented using examples from a broad range of microbes whenever possible.
用于检测外源性和内源性配体的模式识别受体（PRR）可溶性融合蛋白的应用，有助于明确PRR在针对病原体的固有免疫反应中的作用、它们如何塑造适应性免疫反应以及在维持体内平衡中的功能。将免疫球蛋白（Ig）可结晶片段（Fc）结构域用作融合伴侣，PRR融合蛋白具有可溶性、稳定性好、易于纯化的特点，由于Fc同源二聚化特性而具有更高的亲和力，因此已被广泛应用于多种领域，如流式细胞术、蛋白质和聚糖阵列筛选以及免疫荧光显微镜检查。本综述将主要聚焦于PRR中C型凝集素受体（CLR）亚组的细胞膜表达聚糖结合蛋白对病原体的识别。PRR与保守的病原体相关分子模式（PAMP）结合，如通常位于病原体内部或外表面的聚糖。值得注意的是，许多聚糖结构在宿主和病原体上是相同的（例如Lewis（Le）X聚糖），这使得使用具有已知内源性和/或外源性配体的Fc CLR融合蛋白作为工具来识别能够与免疫系统相互作用的病原体结构成为可能。对高度纯化的病原体衍生细胞壁成分的筛选，已能够鉴定出许多被CLR识别的独特PAMP结构。本综述重点介绍了使用Fc CLR融合蛋白的研究，着重阐述了在真菌、细菌、病毒和寄生虫中发现的PAMP。只要有可能，就会使用来自广泛微生物的例子来介绍不同CLR家族的结构和独特特征。
