Cargando…

Arginase-1 Is Responsible for IL-13-Mediated Susceptibility to Trypanosoma cruzi Infection

Arginase-1 (Arg-1) is a marker for alternatively activated macrophages (AAM) and is mainly induced by the type 2 cytokines interleukin (IL)-4 and IL-13 through the common IL-4 receptor-alpha (Rα) subunit. Both, Arg-1 and AAM undermine macrophage effector functions against intracellular parasites and...

Descripción completa

Detalles Bibliográficos
Autores principales: Abad Dar, Mahin, Hölscher, Christoph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281981/
https://www.ncbi.nlm.nih.gov/pubmed/30555475
http://dx.doi.org/10.3389/fimmu.2018.02790
_version_ 1783378902555557888
author Abad Dar, Mahin
Hölscher, Christoph
author_facet Abad Dar, Mahin
Hölscher, Christoph
author_sort Abad Dar, Mahin
collection PubMed
description Arginase-1 (Arg-1) is a marker for alternatively activated macrophages (AAM) and is mainly induced by the type 2 cytokines interleukin (IL)-4 and IL-13 through the common IL-4 receptor-alpha (Rα) subunit. Both, Arg-1 and AAM undermine macrophage effector functions against intracellular parasites and are therefore implicated in the susceptibility to infection with Trypanosoma cruzi, the causative agent of Chagas' disease. However, the involvement of Arg-1 in promoting intracellular replication of T. cruzi in AAM has not been proven so far in vivo. Because Arg-1 is only moderately expressed in T. cruzi-infected wildtype mice, we elucidated the role of Arg-1 and AAM during infection in IL-13-overexpressing (IL-13(tg)) mice, which are characterized by an inflammation-induced development of AAM and an accompanied elevated expression of Arg-1. In comparison to wildtype littermates, IL-13(tg) mice were highly susceptible to T. cruzi infection with enhanced parasitemia and impaired survival. Importantly, T. cruzi-infected IL-13(tg) mice developed an elevated alternative macrophage activation with increased arginase activity. To proof the hypothesis, that Arg-1 accounts for the increased susceptibility of IL-13(tg) mice, we blocked arginase activity in infected IL-13(tg) mice. Because this arginase inhibition resulted in a decreased susceptibility to experimental Chagas disease our study supports in summary the conclusion that IL-13/IL-4Rα-driven Arg-1 expression contributes to the permissiveness of the host to T. cruzi infection.
format Online
Article
Text
id pubmed-6281981
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-62819812018-12-14 Arginase-1 Is Responsible for IL-13-Mediated Susceptibility to Trypanosoma cruzi Infection Abad Dar, Mahin Hölscher, Christoph Front Immunol Immunology Arginase-1 (Arg-1) is a marker for alternatively activated macrophages (AAM) and is mainly induced by the type 2 cytokines interleukin (IL)-4 and IL-13 through the common IL-4 receptor-alpha (Rα) subunit. Both, Arg-1 and AAM undermine macrophage effector functions against intracellular parasites and are therefore implicated in the susceptibility to infection with Trypanosoma cruzi, the causative agent of Chagas' disease. However, the involvement of Arg-1 in promoting intracellular replication of T. cruzi in AAM has not been proven so far in vivo. Because Arg-1 is only moderately expressed in T. cruzi-infected wildtype mice, we elucidated the role of Arg-1 and AAM during infection in IL-13-overexpressing (IL-13(tg)) mice, which are characterized by an inflammation-induced development of AAM and an accompanied elevated expression of Arg-1. In comparison to wildtype littermates, IL-13(tg) mice were highly susceptible to T. cruzi infection with enhanced parasitemia and impaired survival. Importantly, T. cruzi-infected IL-13(tg) mice developed an elevated alternative macrophage activation with increased arginase activity. To proof the hypothesis, that Arg-1 accounts for the increased susceptibility of IL-13(tg) mice, we blocked arginase activity in infected IL-13(tg) mice. Because this arginase inhibition resulted in a decreased susceptibility to experimental Chagas disease our study supports in summary the conclusion that IL-13/IL-4Rα-driven Arg-1 expression contributes to the permissiveness of the host to T. cruzi infection. Frontiers Media S.A. 2018-11-29 /pmc/articles/PMC6281981/ /pubmed/30555475 http://dx.doi.org/10.3389/fimmu.2018.02790 Text en Copyright © 2018 Abad Dar and Hölscher. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Abad Dar, Mahin
Hölscher, Christoph
Arginase-1 Is Responsible for IL-13-Mediated Susceptibility to Trypanosoma cruzi Infection
title Arginase-1 Is Responsible for IL-13-Mediated Susceptibility to Trypanosoma cruzi Infection
title_full Arginase-1 Is Responsible for IL-13-Mediated Susceptibility to Trypanosoma cruzi Infection
title_fullStr Arginase-1 Is Responsible for IL-13-Mediated Susceptibility to Trypanosoma cruzi Infection
title_full_unstemmed Arginase-1 Is Responsible for IL-13-Mediated Susceptibility to Trypanosoma cruzi Infection
title_short Arginase-1 Is Responsible for IL-13-Mediated Susceptibility to Trypanosoma cruzi Infection
title_sort arginase-1 is responsible for il-13-mediated susceptibility to trypanosoma cruzi infection
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281981/
https://www.ncbi.nlm.nih.gov/pubmed/30555475
http://dx.doi.org/10.3389/fimmu.2018.02790
work_keys_str_mv AT abaddarmahin arginase1isresponsibleforil13mediatedsusceptibilitytotrypanosomacruziinfection
AT holscherchristoph arginase1isresponsibleforil13mediatedsusceptibilitytotrypanosomacruziinfection