Innate and Adaptive Immune Responses Following PD-L1 Blockade in Treating Chronic Murine Alveolar Echinococcosis

Background: Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) immune checkpoint blockade are efficacious in certain cancer therapies.

Objectives: The present study aimed to provide a picture about the development of innate and adaptive immune responses upon PD-L1 blockade in treating chronic murine AE.

Methods: Immune treatment started at 6 weeks post-E. multilocularis infection, and was maintained for 8 weeks with twice per week anti-PD-L1 administration (intraperitoneal). The study included an outgroup-control with mice perorally medicated with albendazole 5 d/wk, and another one with both treatments combined. Assessment of treatment efficacy was based on determining parasite weight, innate and adaptive immune cell profiles, histopathology and liver tissue cytokine levels.

Results/conclusions: Findings showed that the parasite load was significantly reduced in response to PD-L1 blockade, and this blockade (a) contributed to T-cell activity by increasing CD4 /CD8 effector T cells, and decreasing Tregs; (b) had the capacity to restore DCs and Kupffer cells/Macrophages; (c) suppressed NKT and NK cells; and thus (d) lead to an improved control of E. multilocularis infection in mice. This study suggests that the PD-L1 pathway plays an important role by regulating adaptive and innate immune cells against E. multilocularis infection, with significant modulation of tissue inflammation.