Echinococcus multilocularis vesicular fluid induces the expression of immune checkpoint proteins in vitro

Aims 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). Methods and Results 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). Conclusion These preliminary data suggest that immune checkpoints could be a way for E. multilocularis to modulate the host immune response during alveolar echinococcosis.