Parasitology Mycology Department, Jean Minjoz University Hospital, Besancon, France.
Echinococcosis National Reference Center, Besancon, France.
Parasite Immunol. 2020 Jun;42(6):e12711. doi: 10.1111/pim.12711.
Alveolar echinococcosis is a severe chronic helminthic infection that mimics a tumour-like disease. This study aimed at investigating in vitro interactions between Echinococcus multilocularis vesicular fluid (VF) and different immune checkpoints (PD-1/PD-L1, CTLA-4, LAG-3 and TIM-3).
Peripheral blood mononuclear cells (PBMC) from healthy blood donors were isolated by Ficoll. Natural killer (NK) cells were selected. Each type of cell was stimulated individually with E. multilocularis-VF. Expression of the different immune checkpoints was measured by flow cytometry on day 3 and day 6; all supernatants were used for immunoassays. Cells and supernatants from 22 healthy donors were analysed. A significant increase of PD-1, PD-L1, LAG-3 and TIM-3 was observed upon E. multilocularis-VF exposure for NK cells on day 3 (P < .05, Wilcoxon signed-rank test). A significant increase of PD-L1 and CTLA-4 was observed upon E. multilocularis-VF exposure for T cells on day 6 (P < .05, Wilcoxon signed-rank test), which was associated with increased levels of Th1 and Th2 cytokines P < .05, Wilcoxon signed-rank test).
These preliminary data suggest that immune checkpoints could be a way for E. multilocularis to modulate the host immune response during alveolar echinococcosis.
泡型包虫病是一种严重的慢性寄生虫感染,其表现类似于肿瘤样疾病。本研究旨在研究细粒棘球蚴囊液(VF)与不同免疫检查点(PD-1/PD-L1、CTLA-4、LAG-3 和 TIM-3)之间的体外相互作用。
用 Ficoll 分离健康献血者的外周血单核细胞(PBMC)。选择自然杀伤(NK)细胞。用 E. multilocularis-VF 分别刺激每种类型的细胞。在第 3 天和第 6 天通过流式细胞术测量不同免疫检查点的表达;所有上清液均用于免疫测定。分析了 22 名健康供体的细胞和上清液。在第 3 天,NK 细胞暴露于 E. multilocularis-VF 后,PD-1、PD-L1、LAG-3 和 TIM-3 的表达明显增加(P <.05,Wilcoxon 符号秩检验)。在第 6 天,T 细胞暴露于 E. multilocularis-VF 后,PD-L1 和 CTLA-4 的表达明显增加(P <.05,Wilcoxon 符号秩检验),这与 Th1 和 Th2 细胞因子水平升高有关(P <.05,Wilcoxon 符号秩检验)。
这些初步数据表明,免疫检查点可能是细粒棘球蚴在泡型包虫病期间调节宿主免疫反应的一种方式。