Antigen-presenting cells (APCs) are present throughout the human body—in tissues, at barrier sites and in the circulation. They are critical for processing external signals to instruct both local and systemic responses toward immune tolerance or immune defense. APCs express an extensive repertoire of pattern-recognition receptors (PRRs) to detect and transduce these signals. C-type lectin receptors (CLRs) comprise a subfamily of PRRs dedicated to sensing glycans, including those expressed by commensal and pathogenic bacteria. This review summarizes recent findings on the recognition of and responses to bacteria by membrane-expressed CLRs on different APC subsets, which are discussed according to the primary site of infection. Many CLR-bacterial interactions promote bacterial clearance, whereas other interactions are exploited by bacteria to enhance their pathogenic potential. The discrimination between protective and virulence-enhancing interactions is essential to understand which interactions to target with new prophylactic or treatment strategies. CLRs are also densely concentrated at APC dendrites that sample the environment across intact barrier sites. This suggests an–as yet–underappreciated role for CLR-mediated recognition of microbiota-produced glycans in maintaining tolerance at barrier sites. In addition to providing a concise overview of identified CLR-bacteria interactions, we discuss the main challenges and potential solutions for the identification of new CLR-bacterial interactions, including those with commensal bacteria, and for in-depth structure-function studies on CLR-bacterial glycan interactions. Finally, we highlight the necessity for more relevant tissue-specific in vitro, in vivo and ex vivo models to develop therapeutic applications in this area.

抗原呈递细胞 (APC) 存在于整个人体——组织中、屏障部位和循环中。它们对于处理外部信号以指导局部和全身反应对免疫耐受或免疫防御至关重要。APC 表达大量模式识别受体 (PRR) 以检测和转导这些信号。C 型凝集素受体 (CLR) 包含一个 PRR 亚家族，专门用于感知聚糖，包括由共生菌和病原菌表达的聚糖。这篇综述总结了最近关于不同 APC 亚群上膜表达 CLR 对细菌的识别和反应的发现，这些发现是根据感染的主要部位进行讨论的。许多 CLR-细菌相互作用促进细菌清除，而细菌利用其他相互作用来增强其致病潜力。区分保护性相互作用和毒力增强相互作用对于了解新的预防或治疗策略要针对哪些相互作用至关重要。CLRs 也密集地集中在 APC 树突上，这些树突在完整的屏障位点对环境进行采样。这表明 CLR 介导的对微生物群产生的聚糖的识别在维持屏障位点耐受性方面的作用尚未得到充分认识。除了简要概述已识别的 CLR-细菌相互作用外，我们还讨论了识别新的 CLR-细菌相互作用的主要挑战和潜在解决方案，包括与共生细菌的相互作用，以及对 CLR-的深入结构-功能研究。细菌聚糖相互作用。最后，体外，体内和离体在该领域开发治疗应用的模型。