Digest the Sugar, Kill the Parasite: A New Experimental Concept in Treating Alveolar Echinococcosis.

Wang, Junhua; von Gunten, Stephan; Beldi, Guido; Grandgirard, Denis; Leib, Stephen L.; Gottstein, Bruno (2021). Digest the Sugar, Kill the Parasite: A New Experimental Concept in Treating Alveolar Echinococcosis. Pharmacology, 106(1-2), pp. 3-8. Karger 10.1159/000509355

[img] Text
von Gunten_Digest the Sugar, Kill the Parasite.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (450kB) | Request a copy

INTRODUCTION

The E. multilocularis laminated layer (LL) is a heavily glycosylated parasitic structure that plays an important role in protecting the larval stage (metacestode) of this parasite from physiological and immunological host reactions. We elaborated an experimental design with the idea to modify the (glycan) surface of the LL by a targeted digestion. This should allow the host defense to more easily recognize and attack (or kill) the parasite by immune-mediated effects.

METHODS

Experimentally, E. multilocularis (clone H95) metacestodes were cultured in vitro with or without addition of α1-3,4,6-galactosidase or β1-3-galactosidase in the medium. Morphological changes were subsequently measured by microscopy at different time points. Parasites were then recovered at day 5 and reinjected into mice for assessing their viability and infectious status. For finally recovered parasites, the respective load was assessed ex vivo by wet weight measurement, and host-related PD1 and IL-10 levels were determined as the key immunoregulators by using flow cytometry.

RESULTS

Our experiments demonstrated that the parasite vesicular structure can be directly destroyed by adding galactosidases into the in vitro culture system, resulting in the fact that the parasite metacestode vesicles could not anymore infect and develop in mice after this glycan digestion. Moreover, when compared to the mice inoculated with E. multilocularis metacestode without galactosidases, PD1 expression was upregulated in CD4+ Teffs from mice inoculated with E. multilocularis metacestode pretreated with β1-3-galactosidase, with a lower IL-10 secretion from CD4+ Teffs; there was no difference of PD1 and IL-10 expression levels regarding CD4+ Teff from mice inoculated with E. multilocularis metacestode pretreated with α1-3,4,6-galac-tosidase.

DISCUSSION

We raised our hypothesis that this "aborting" effect may be linked to an altered PD1 and IL-10 response fine-tuning between immunopathology and immune protection. These findings justify a continuation of these experiments upon therapeutical in vivo administration of the enzymes.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > 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 Parasitology
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Wang, Junhua; von Gunten, Stephan; Beldi, Guido; Grandgirard, Denis; Leib, Stephen and Gottstein, Bruno

Subjects:

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

ISSN:

0031-7012

Publisher:

Karger

Language:

English

Submitter:

Celine Joray

Date Deposited:

25 Nov 2020 16:17

Last Modified:

06 Feb 2021 01:32

Publisher DOI:

10.1159/000509355

PubMed ID:

32739918

Uncontrolled Keywords:

Echinococcus multilocularis Galactosidase Glycan PD1

BORIS DOI:

10.7892/boris.148496

URI:

https://boris.unibe.ch/id/eprint/148496

Actions (login required)

Edit item Edit item
Provide Feedback