Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/13187
Title: Cruzipain Activates Latent TGF-β from Host Cells during T. cruzi Invasion
Authors: Ferrão, Patrícia Mello
Levy, Claudia Masini d'Avila
Araujo-Jorge, Tania C.
Degrave, Wim Maurits
Gonçalves, Antônio da Silva
Garzoni, Luciana Ribeiro
Lima, Ana Paula
Feige, Jean Jacques
Bailly, Sabine
Lima, Leila Mendonça
Waghabi, Mariana Caldas
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biotecnologia e Fisiologia de Infecções Virais. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Programa Integrado de Doença de Chagas. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofisica Carlos Chagas Filho. Laboratório de Bioquímica e Biologia Molecular de Peptidases. Rio de Janeiro, RJ, Brasil.
INSERM, Unité 1036, Grenoble, F-38054, France / Université Grenoble-Alpes—Grenoble, F-38041, France, CEA, DSV,iRTSV, Laboratory of Biology of Cancer and Infection, Grenoble, F-38054, France.
INSERM, Unité 1036, Grenoble, F-38054, France / Université Grenoble-Alpes—Grenoble, F-38041, France, CEA, DSV,iRTSV, Laboratory of Biology of Cancer and Infection, Grenoble, F-38054, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Programa Integrado de Doença de Chagas. Rio de Janeiro, RJ, Brasil.
Abstract: Several studies indicate that the activity of cruzipain, the main lysosomal cysteine peptidase of Trypanosoma cruzi, contributes to parasite infectivity. In addition, the parasitic invasion process of mammalian host cells is described to be dependent on the activation of the host TGF-β signaling pathway by T. cruzi. Here, we tested the hypothesis that cruzipain could be an important activator of latent TGF-β and thereby trigger TGF-β-mediated events crucial for the development of Chagas disease. We found that live epimastigotes of T. cruzi, parasite lysates and purified cruzipain were able to activate latent TGF-β in vitro. This activation could be inhibited by the cysteine peptidase inhibitor Z-Phe-Ala-FMK. Moreover, transfected parasites overexpressing chagasin, a potent endogenous cruzipain inhibitor, prevented latent TGF-β activation. We also observed that T. cruzi invasion, as well as parasite intracellular growth, were inhibited by the administration of Z-Phe-Ala-FMK or anti-TGF-β neutralizing antibody to Vero cell cultures. We further demonstrated that addition of purified cruzipain enhanced the invasive activity of trypomastigotes and that this effect could be completely inhibited by addition of a neutralizing anti-TGF-β antibody. Taken together, these results demonstrate that the activities of cruzipain and TGF-β in the process of cell invasion are functionally linked. Our data suggest that cruzipain inhibition is an interesting chemotherapeutic approach for Chagas disease not only because of its trypanocidal activity, but also due to the inhibitory effect on TGF-β activation.
Keywords: Trypanosoma cruzi
Chagas Disease
TGF-β
Host Cells
Cruzipain
DeCS: Trypanosoma cruzi
Doença de Chagas
Issue Date: 2015
Publisher: Public Library of Science
Citation: FERRÃO, Patrícia Mello; et al. Cruzipain Activates Latent TGF-β from Host Cells during T. cruzi Invasion. Plos One, v.10, n.5, e0124832, 15p, May 2015.
DOI: 10.1371/journal.pone.0124832
ISSN: 1932-6203
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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