Innate and adaptive immune responses following PD-L1 blockade in treating chronic murine alveolar echinococcosis
Fadi Jebbawi1, Anne-Pauline Bellanger2,3, Britta Lunström-Stadelmann4
1Department of Visceral Surgery and Medicine, Inselspital, University Hospital of Bern, Bern, Switzerland.
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.
Insights
Programmed death-ligand 1 (PD-L1) blockade reduced parasite load in mice with chronic infection. This immunotherapy enhanced T-cell activity and restored key immune cells, improving infection control.
Area of Science:
- Immunology
- Parasitology
- Pharmacology
Background:
- Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) immune checkpoint blockade demonstrate efficacy in various cancer treatments.
- Understanding the impact of PD-L1 blockade on immune responses is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate the development of innate and adaptive immune responses following PD-L1 blockade in a murine model of chronic Echinococcus multilocularis (E. multilocularis) infection.
- To evaluate the therapeutic efficacy of anti-PD-L1 treatment, alone and in combination with albendazole, in controlling E. multilocularis infection.
Main Methods:
- Mice with chronic E. multilocularis infection received intraperitoneal anti-PD-L1 treatment twice weekly for 8 weeks.
- Control groups included mice treated with albendazole or a combination of anti-PD-L1 and albendazole.
- Treatment efficacy was assessed by measuring parasite weight, analyzing immune cell profiles (CD4+, CD8+, Tregs, DCs, Kupffer cells, Macrophages, NKT, NK cells), histopathology, and liver tissue cytokine levels.
Main Results:
- PD-L1 blockade significantly reduced parasite load.
- Treatment increased CD4+/CD8+ effector T cells and decreased regulatory T cells (Tregs).
- PD-L1 blockade restored dendritic cells (DCs) and Kupffer cells/Macrophages, while suppressing NKT and NK cells, leading to improved control of E. multilocularis infection.
Conclusions:
- The PD-L1 pathway plays a significant role in regulating adaptive and innate immune responses against E. multilocularis infection.
- PD-L1 blockade modulates tissue inflammation and enhances immune control, suggesting its potential as a therapeutic target for echinococcosis.
