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TGF-β and TGF-β/Smad Signaling in the Interactions between Echinococcus multilocularis and Its Hosts

Alveolar echinococcosis (AE) is characterized by the development of irreversible fibrosis and of immune tolerance towards Echinococcus multilocularis (E. multilocularis). Very little is known on the presence of transforming growth factor-β (TGF-β) and other components of TGF-β/Smad pathway in the li...

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Autores principales: Wang, Junhua, Zhang, Chuanshan, Wei, Xufa, Blagosklonov, Oleg, Lv, Guodong, Lu, Xiaomei, Mantion, Georges, Vuitton, Dominique A., Wen, Hao, Lin, Renyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566151/
https://www.ncbi.nlm.nih.gov/pubmed/23405141
http://dx.doi.org/10.1371/journal.pone.0055379
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author Wang, Junhua
Zhang, Chuanshan
Wei, Xufa
Blagosklonov, Oleg
Lv, Guodong
Lu, Xiaomei
Mantion, Georges
Vuitton, Dominique A.
Wen, Hao
Lin, Renyong
author_facet Wang, Junhua
Zhang, Chuanshan
Wei, Xufa
Blagosklonov, Oleg
Lv, Guodong
Lu, Xiaomei
Mantion, Georges
Vuitton, Dominique A.
Wen, Hao
Lin, Renyong
author_sort Wang, Junhua
collection PubMed
description Alveolar echinococcosis (AE) is characterized by the development of irreversible fibrosis and of immune tolerance towards Echinococcus multilocularis (E. multilocularis). Very little is known on the presence of transforming growth factor-β (TGF-β) and other components of TGF-β/Smad pathway in the liver, and on their possible influence on fibrosis, over the various stages of infection. Using Western Blot, qRT-PCR and immunohistochemistry, we measured the levels of TGF-β1, TGF-β receptors, and down-stream Smads activation, as well as fibrosis marker expression in both a murine AE model from day 2 to 360 post-infection (p.i.) and in AE patients. TGF-β1, its receptors, and down-stream Smads were markedly expressed in the periparasitic infiltrate and also in the hepatocytes, close to and distant from AE lesions. Fibrosis was significant at 180 days p.i. in the periparasitic infiltrate and was also present in the liver parenchyma, even distant from the lesions. Over the time course after infection TGF-β1 expression was correlated with CD4/CD8 T-cell ratio long described as a hallmark of AE severity. The time course of the various actors of the TGF-β/Smad system in the in vivo mouse model as well as down-regulation of Smad7 in liver areas close to the lesions in human cases highly suggest that TGF-β plays an important role in AE both in immune tolerance against the parasite and in liver fibrosis.
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spelling pubmed-35661512013-02-12 TGF-β and TGF-β/Smad Signaling in the Interactions between Echinococcus multilocularis and Its Hosts Wang, Junhua Zhang, Chuanshan Wei, Xufa Blagosklonov, Oleg Lv, Guodong Lu, Xiaomei Mantion, Georges Vuitton, Dominique A. Wen, Hao Lin, Renyong PLoS One Research Article Alveolar echinococcosis (AE) is characterized by the development of irreversible fibrosis and of immune tolerance towards Echinococcus multilocularis (E. multilocularis). Very little is known on the presence of transforming growth factor-β (TGF-β) and other components of TGF-β/Smad pathway in the liver, and on their possible influence on fibrosis, over the various stages of infection. Using Western Blot, qRT-PCR and immunohistochemistry, we measured the levels of TGF-β1, TGF-β receptors, and down-stream Smads activation, as well as fibrosis marker expression in both a murine AE model from day 2 to 360 post-infection (p.i.) and in AE patients. TGF-β1, its receptors, and down-stream Smads were markedly expressed in the periparasitic infiltrate and also in the hepatocytes, close to and distant from AE lesions. Fibrosis was significant at 180 days p.i. in the periparasitic infiltrate and was also present in the liver parenchyma, even distant from the lesions. Over the time course after infection TGF-β1 expression was correlated with CD4/CD8 T-cell ratio long described as a hallmark of AE severity. The time course of the various actors of the TGF-β/Smad system in the in vivo mouse model as well as down-regulation of Smad7 in liver areas close to the lesions in human cases highly suggest that TGF-β plays an important role in AE both in immune tolerance against the parasite and in liver fibrosis. Public Library of Science 2013-02-06 /pmc/articles/PMC3566151/ /pubmed/23405141 http://dx.doi.org/10.1371/journal.pone.0055379 Text en © 2013 Wang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wang, Junhua
Zhang, Chuanshan
Wei, Xufa
Blagosklonov, Oleg
Lv, Guodong
Lu, Xiaomei
Mantion, Georges
Vuitton, Dominique A.
Wen, Hao
Lin, Renyong
TGF-β and TGF-β/Smad Signaling in the Interactions between Echinococcus multilocularis and Its Hosts
title TGF-β and TGF-β/Smad Signaling in the Interactions between Echinococcus multilocularis and Its Hosts
title_full TGF-β and TGF-β/Smad Signaling in the Interactions between Echinococcus multilocularis and Its Hosts
title_fullStr TGF-β and TGF-β/Smad Signaling in the Interactions between Echinococcus multilocularis and Its Hosts
title_full_unstemmed TGF-β and TGF-β/Smad Signaling in the Interactions between Echinococcus multilocularis and Its Hosts
title_short TGF-β and TGF-β/Smad Signaling in the Interactions between Echinococcus multilocularis and Its Hosts
title_sort tgf-β and tgf-β/smad signaling in the interactions between echinococcus multilocularis and its hosts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566151/
https://www.ncbi.nlm.nih.gov/pubmed/23405141
http://dx.doi.org/10.1371/journal.pone.0055379
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