High PD-1 and CTLA-4 expression correlates with host immune suppression in patients and a mouse model infected with Echinococcus multilocularis.

Autor: Sun T; Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China., Yang Y; Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China., Qiu Y; Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China., Wang T; Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China., Yang M; Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China., Shen S; Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China., Wang W; Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China. wwtdoctor02@163.com.
Jazyk: angličtina
Zdroj: Parasites & vectors [Parasit Vectors] 2024 Oct 25; Vol. 17 (1), pp. 437. Date of Electronic Publication: 2024 Oct 25.
DOI: 10.1186/s13071-024-06511-2
Abstrakt: Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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