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 chr...

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Published in:Parasite immunology 2021-08, Vol.43 (8), p.e12834-n/a
Main Authors: Jebbawi, Fadi, Bellanger, Anne‐Pauline, Lunström‐Stadelmann, Britta, Rufener, Reto, Dosch, Michel, Goepfert, Christine, Gottstein, Bruno, Millon, Laurence, Grandgirard, Denis, Leib, Stephen L., Beldi, Guido, Wang, Junhua
Format: Article
Language:English
Subjects:
Adaptive immunity
Albendazole
Alveoli
anti‐PD‐L1
Apoptosis
CD4 antigen
CD8 antigen
Cytokines
Echinococcosis
Echinococcus multilocularis
Ecology, environment
Effector cells
Health
Hepatocytes
Immune checkpoint
immunotherapy
Infections
Kupffer cells
Life Sciences
Lymphocytes T
Macrophages
Parasites
PD-1 protein
PD-L1 protein
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Summary: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.
ISSN:0141-9838
1365-3024
DOI:10.1111/pim.12834