Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Department of Pediatrics, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, China.
Acta Biochim Biophys Sin (Shanghai). 2021 Oct 12;53(10):1290-1299. doi: 10.1093/abbs/gmab107.
Clostridioides difficile infection (CDI) is a common infection of the gastrointestinal tract. Typically, 20%-30% of CDI patients experience recurrent C.difficile infection (RCDI). Although the role of Th17 in infectious and inflammatory diseases including CDI has gained attention, reports on the correlation between Th17 and RCDI are scarce. In this study, CDI and RCDI mice models were challenged with C. difficile. Serum lactic acid dehydrogenase, inflammatory factor levels, reverse transcriptase-polymerase chain reaction, western blot analysis, hematoxylin and eosin staining, immunohistochemistry, flow cytometry analysis, and enzyme-linked immunosorbent assay were performed on the CDI, RCDI, and control group mice. The results showed more serious clinical manifestations in the RCDI group compared with those in the CDI group. More severe gut barrier disruption and higher degree of microbiota translocation were observed in the RCDI group compared with those in the CDI group. Moreover, extremely severe apoptosis was observed in HCT-116 cells incubated with the serum from RCDI mice model. In addition, higher levels of Th17 and IL-17 were detected in the blood or serum from the RCDI mouse model. Treatment with RORγt small molecule inhibitor SR1001 increased the expression of occludin, decreased the apoptotic rate of HCT-116 cells, and decreased the concentrations of Th17 and IL-17. Concisely, Th17 and IL-17 are potential indicators of RCDI and may serve as therapeutic targets for RCDI treatment. This study lays the foundation for future research on RCDI diagnosis and treatment.
艰难梭菌感染（CDI）是一种常见的胃肠道感染。通常，20%-30%的 CDI 患者会经历复发性艰难梭菌感染（RCDI）。尽管 Th17 在包括 CDI 在内的感染性和炎症性疾病中的作用已引起关注，但关于 Th17 与 RCDI 之间相关性的报道却很少。在这项研究中，用艰难梭菌对 CDI 和 RCDI 小鼠模型进行了挑战。对 CDI、RCDI 和对照组小鼠进行了血清乳酸脱氢酶、炎症因子水平、逆转录-聚合酶链反应、western blot 分析、苏木精和伊红染色、免疫组织化学、流式细胞术分析和酶联免疫吸附测定。结果表明，RCDI 组的临床症状比 CDI 组更为严重。与 CDI 组相比，RCDI 组的肠道屏障破坏更为严重，细菌移位程度更高。此外，在与 RCDI 小鼠模型血清孵育的 HCT-116 细胞中观察到极其严重的细胞凋亡。此外，在 RCDI 小鼠模型的血液或血清中检测到更高水平的 Th17 和 IL-17。用 RORγt 小分子抑制剂 SR1001 治疗可增加紧密连接蛋白的表达，降低 HCT-116 细胞的凋亡率，并降低 Th17 和 IL-17 的浓度。简而言之，Th17 和 IL-17 是 RCDI 的潜在指标，可能成为 RCDI 治疗的靶点。这项研究为未来 RCDI 的诊断和治疗研究奠定了基础。
