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 is 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 five days/week, 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 re-store 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.