Clostridioides difficile （CD）是引起抗生素相关性腹泻和假性膜性肠炎的主要原因。C. difficile感染（CDI）在社区中呈逐渐增加的趋势，并对医疗保健系统造成了重要负担。急需从对其分子发病机制更好的理解中，确定新的基于免疫的治疗靶点。Toll样受体7（TLR7）是一种重要的模式识别受体，作为免疫传感器发挥作用，能引发宿主对病原体的防御反应，但TLR7与CDI的关系尚不清楚。在这里，我们报告了在CDI患者和小鼠中，TLR7的表达水平显著增加。CDI小鼠中TLR7的缺失表现出增强的肠道内容物细菌清除能力，减少肠道炎症、水肿、损伤，并延长存活时间。TLR7缺失降低了肠道中肿瘤坏死因子（TNF）-α、干扰素（IFN）-γ和IFN-α1的浓度，改善了组织损伤和炎症。流式细胞仪和免疫荧光结果表明，TLR7增强了感染肠道中白细胞的募集。体外实验结果显示，TLR7削弱了巨噬细胞对CD的吞噬和杀菌能力，促进了反应性氧化物产生，并加速了细胞凋亡。据我们所知，我们的研究首次将TLR7确定为造成CDI的免疫病理的关键因素，提示靶向TLR7可能是CDI的潜在治疗方法。版权所有©2023，由Elsevier Masson SAS出版。

Clostridioides difficile (CD) is a major cause of antibiotic-associated diarrhea and pseudomembranous enteritis. C. difficile infection (CDI) is increasingly present in the community and represents a significant burden on the healthcare system. Identification of novel immune-based therapeutic targets from a better understanding of their molecular pathogenesis is urgently required. Toll-like receptor 7 (TLR7) is an important pattern recognition receptor and function as an immune sensor that can trigger host defenses against pathogens, but the relationship between TLR7 and CDI remains unknown. Here, we reported that the expression levels of TLR7 increased significantly in patients and mice with CDI. Absence of TLR7 in mice with CDI demonstrated enhanced bacterial clearance of intestinal contents and reduced intestinal inflammation, edema, injury and prolonged the survival. TLR7 loss decreased the concentrations of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IFN-α1 in the intestine and improved tissue damage and inflammation. Flow cytometry and immunofluorescence results indicated that TLR7 enhanced leukocyte recruitment in the infected intestine. In-vitro results have shown that TLR7 impairs the phagocytosis and killing ability of macrophages to CD, prompts reactive oxygen species (ROS) production and accelerates apoptosis. To our knowledge, our study first identified TLR7 as a critical factor that contributes to the immunopathology of CDI, suggesting that targeting TLR7 might serve as a potential treatment for CDI.Copyright © 2023. Published by Elsevier Masson SAS.