Innate and adaptive immune responses following PD-L1 blockade in treating chronic murine alveolar echinococcosis.

Jebbawi, Fadi; Bellanger, Anne-Pauline; Lundström-Stadelmann, Britta; Rufener, Reto; Dosch, Michel; Goepfert, Christine; Gottstein, Bruno; Millon, Laurence; Grandgirard, Denis; Leib, Stephen L.; Beldi, Guido; Wang, Junhua (2021). Innate and adaptive immune responses following PD-L1 blockade in treating chronic murine alveolar echinococcosis. Parasite immunology, 43(8), e12834. Wiley 10.1111/pim.12834

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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.

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