Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Parasit Vectors. 2024 Oct 25;17(1):437. doi: 10.1186/s13071-024-06511-2.
Alveolar echinococcosis (AE), a fatal disease caused by Echinococcus multilocularis, often affects the liver, with tumor-like growth. However, the mechanism by which E. multilocularis evades host immune surveillance remains unclear.
We collected liver specimens from hepatic alveolar echinococcosis (HAE) patients and established a mouse model of E. multilocularis infection. Immunofluorescence staining and flow cytometry were performed to analyze programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte associated antigen 4 (CTLA-4) expression in human samples, while flow cytometry and quantitative real-time polymerase chain reaction (PCR) were performed for similar analyses in mouse samples. Cell proliferation and protoscolex (PSC) killing assays were designed to explore how E. multilocularis induces host immunosuppression.
An inflammatory reaction band with high PD-1 and CTLA-4 expression was found in close liver tissue (CLT). The ratio of regulatory T cells (Tregs) was higher in CLT than in distant liver tissue (DLT), and Tregs in CLT tended to express higher levels of PD-1 and CTLA-4 than those in DLT from HAE patients. Echinococcus multilocularis-infected mice showed significantly elevated expression of PD-1 and CTLA-4 on splenocytes and peritoneal cells. PD-1/PD-L1 or CTLA-4 pathway blockade could relieve the immunosuppressive effects of Tregs from infected mice and enhance PSC killing by mouse splenocytes.
E. multilocularis regulated the function of T cells via the PD-1/PD-L1- and CTLA-4-dependent pathways and subsequently evaded host immune attacks. These findings provide insights for investigating the pathogenic mechanism of AE.
泡型包虫病（AE）是由多房棘球绦虫引起的一种致命疾病，常累及肝脏，呈肿瘤样生长。然而，多房棘球蚴逃避宿主免疫监视的机制尚不清楚。
我们收集了肝泡型包虫病（HAE）患者的肝脏标本，并建立了多房棘球蚴感染的小鼠模型。通过免疫荧光染色和流式细胞术分析人源样本中程序性死亡蛋白 1（PD-1）和细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）的表达，同时通过流式细胞术和实时定量聚合酶链反应（PCR）对小鼠样本进行类似分析。设计了细胞增殖和原头蚴（PSC）杀伤实验，以探索多房棘球蚴如何诱导宿主免疫抑制。
在紧邻肝组织（CLT）中发现了具有高 PD-1 和 CTLA-4 表达的炎症反应带。CLT 中的调节性 T 细胞（Tregs）比例高于远离肝组织（DLT），并且来自 HAE 患者的 CLT 中的 Tregs 倾向于表达比 DLT 中更高水平的 PD-1 和 CTLA-4。多房棘球蚴感染的小鼠脾细胞和腹腔细胞中 PD-1 和 CTLA-4 的表达明显升高。PD-1/PD-L1 或 CTLA-4 通路阻断可缓解感染小鼠 Tregs 的免疫抑制作用，并增强小鼠脾细胞对 PSC 的杀伤作用。
多房棘球蚴通过 PD-1/PD-L1 和 CTLA-4 依赖途径调节 T 细胞的功能，从而逃避宿主的免疫攻击。这些发现为研究 AE 的发病机制提供了思路。
