Depletion of FoxP3+ Tregs improves control of larval Echinococcus multilocularis infection by promoting co-stimulation and Th1/17 immunity.

Wang, Junhua; Müller, Stefan Jürg; Lin, Renyong; Siffert, Myriam; Vuitton, Dominique A; Wen, Hao; Gottstein, Bruno (2017). Depletion of FoxP3+ Tregs improves control of larval Echinococcus multilocularis infection by promoting co-stimulation and Th1/17 immunity. Immunity, inflammation and disease, 5(4), pp. 435-447. Wiley 10.1002/iid3.181

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INTRODUCTION The growth potential of the tumor-like Echinococcus multilocularis metacestode (causing alveolar echinococcosis, AE) is directly linked to the nature/function of the periparasitic host immune-mediated processes. Previous studies had shown that regulatory T cells (Tregs) become gradually up-regulated in the course of both chronic human and murine AE. Thus we now tackled the role of FoxP3+ Tregs and FoxP3+ -Treg-regulated immune response in contributing to the control of this helminthic infection. METHODS The infection outcome in E. multilocularis-infected DEREG mice was measured upon determining parasite load (wet weight of parasitic metacestode tissue). Flow cytometry and qRT-PCR were used to assess Treg, Th17-, Th1-, Th2-type immune responses and antigen presenting cell activation. RESULTS We showed that E. multilocularis-infected DEREG-mice treated with DT (as compared to infected control DEREG-mice without DT application) exhibited a significantly lower parasite load, associated with a persisting capacity of co-stimulation, and an increased Th1/Th17-polarization. CONCLUSIONS FoxP3+ Tregs appear as one of the key players in immune regulatory processes favoring (i) metacestode survival by inhibiting the maturation potential of co-stimulatory activity and (ii) T cell exhaustion (suppressing Th1/Th17-type immune responses). We showed as well that prospectively, targeting FoxP3+ Tregs could be an option to develop an immunotherapy against AE.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Services > Core Facility Zytometrie-Labor/FACSlab

UniBE Contributor:

Müller, Stefan Jürg and Gottstein, Bruno

Subjects:

600 Technology > 630 Agriculture
500 Science
500 Science > 570 Life sciences; biology

ISSN:

2050-4527

Publisher:

Wiley

Language:

English

Submitter:

Marla Rittiner

Date Deposited:

08 Mar 2018 14:55

Last Modified:

05 Dec 2018 10:13

Publisher DOI:

10.1002/iid3.181

PubMed ID:

28621034

Uncontrolled Keywords:

CD4+ CD25+ Treg Echinococcus multilocularis Foxp3 Th1/Th17 immunity co-stimulation

BORIS DOI:

10.7892/boris.111557

URI:

https://boris.unibe.ch/id/eprint/111557

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