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. (In Press). Parasite immunology, 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Parasitology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine

UniBE Contributor:

Lundström Stadelmann, Britta; Rufener, Reto; Dosch, Michel Ernest Jean-Pierre; Göpfert, Christine; Gottstein, Bruno; Grandgirard, Denis; Leib, Stephen; Beldi, Guido and Wang, Junhua

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1365-3024

Publisher:

Wiley

Funders:

[4] Swiss National Science Foundation ; [UNSPECIFIED] European Union’s Seventh Framework Programme

Language:

English

Submitter:

Stephen Leib

Date Deposited:

08 Apr 2021 14:46

Last Modified:

09 Apr 2021 01:34

Publisher DOI:

10.1111/pim.12834

PubMed ID:

33754355

Uncontrolled Keywords:

Echinococcus multilocularis albendazole anti-PD-L1 immunotherapy

BORIS DOI:

10.48350/154722

URI:

https://boris.unibe.ch/id/eprint/154722

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