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.
(© 2020 John Wiley & Sons Ltd.)