Foxp3 T Regulatory Cells as a Potential Target for Immunotherapy against Primary Infection with Echinococcus multilocularis Eggs.

Wang, Junhua; Cardoso, Rita; Marreros, Nelson; Müller, Norbert; Lundström Stadelmann, Britta; Siffert, Myriam; Vuitton, Dominique A; Boué, Franck; Lin, Renyong; Wen, Hao; Gottstein, Bruno (2018). Foxp3 T Regulatory Cells as a Potential Target for Immunotherapy against Primary Infection with Echinococcus multilocularis Eggs. Infection and immunity, 86(10) American Society for Microbiology 10.1128/IAI.00542-18

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Alveolar echinococcosis (AE) is a lethal disease caused by infection with the metacestode stage of the helminth , which develops into a tumorlike mass in susceptible intermediate hosts. The growth potential of this parasite stage is directly linked to the nature of the surrounding periparasitic immune-mediated processes. In a first step (experiment 1), mice were orally infected with eggs, to be used for assessing the hepatic expression profiles of 15 selected cytokine and chemokine genes related to acquired immunity from 21 to 120 days postinfection. The early stage of infection in immunocompetent animals was marked by a mixed Th1/Th2 immune response, as characterized by the concomitant presence of gamma interferon (IFN-γ) and interleukin-4 (IL-4) and their related chemokines. At the late stage of AE, the profile extended to a combined tolerogenic mode including Foxp3, IL-10, and transforming growth factor beta (TGF-β) as key components. In a second step (experiment 2), the effect of T regulatory cell (Treg) deficiency on metacestode growth was assessed in -infected DEREG (depletion of regulatory T cells) mice upon induction of Treg deficiency with diphtheria toxin (DT). The parasite lesions were significantly smaller in the livers of treated mice than in corresponding control groups. Foxp3 Tregs appear to be one of the key players in immune-regulatory processes favoring metacestode survival by affecting antigen presentation and suppressing Th1-type immune responses. For these reasons, we suggest that affecting Foxp3 Tregs could offer an attractive target in the development of an immunotherapy against AE.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Wang, Junhua; De Amorim Cardoso, Rita Isabel; Marreros Canales, Nelson Antonio; Müller, Norbert; Lundström Stadelmann, Britta; Siffert, Myriam and Gottstein, Bruno

Subjects:

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

ISSN:

0019-9567

Publisher:

American Society for Microbiology

Language:

English

Submitter:

Bruno Gottstein

Date Deposited:

18 Dec 2018 13:52

Last Modified:

12 Feb 2019 11:09

Publisher DOI:

10.1128/IAI.00542-18

PubMed ID:

30037796

Uncontrolled Keywords:

Th1 immunity Treg deficiency alveolar echinococcosis oral infection regulatory T cells

BORIS DOI:

10.7892/boris.122743

URI:

https://boris.unibe.ch/id/eprint/122743

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