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Cyclophilin 19 secreted in the host cell cytosol by Trypanosoma cruzi promotes ROS production required for parasite growth.
Dos Santos, Gregory Pedroso; Abukawa, Fernanda Midori; Souza-Melo, Normanda; Alcântara, Laura Maria; Bittencourt-Cunha, Paula; Moraes, Carolina Borsoi; Jha, Bijay Kumar; McGwire, Bradford S; Moretti, Nilmar Silvio; Schenkman, Sergio.
Afiliação
  • Dos Santos GP; Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
  • Abukawa FM; Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
  • Souza-Melo N; Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
  • Alcântara LM; Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
  • Bittencourt-Cunha P; Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
  • Moraes CB; Departamento de Ciências Farmacêuticas, Universidade Federal de São Paulo, Diadema, SP, Brazil.
  • Jha BK; Division of Infectious Diseases/Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA.
  • McGwire BS; Division of Infectious Diseases/Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA.
  • Moretti NS; Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
  • Schenkman S; Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
Cell Microbiol ; 23(4): e13295, 2021 04.
Article em En | MEDLINE | ID: mdl-33222354
Infection by Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, depends on reactive oxygen species (ROS), which has been described to induce parasite proliferation in mammalian host cells. It is unknown how the parasite manages to increase host ROS levels. Here, we found that intracellular T. cruzi forms release in the host cytosol its major cyclophilin of 19 kDa (TcCyp19). Parasites depleted of TcCyp19 by using CRISPR/Cas9 gene replacement proliferate inefficiently and fail to increase ROS, compared to wild type parasites or parasites with restored TcCyp19 gene expression. Expression of TcCyp19 in L6 rat myoblast increased ROS levels and restored the proliferation of TcCyp19 depleted parasites. These events could also be inhibited by cyclosporin A, (a cyclophilin inhibitor), and by polyethylene glycol-linked to antioxidant enzymes. TcCyp19 was found more concentrated in the membrane leading edges of the host cells in regions that also accumulate phosphorylated p47phox , as observed to the endogenous cyclophilin A, suggesting some mechanisms involved with the translocation process of the regulatory subunit p47phox in the activation of the NADPH oxidase enzymatic complex. We concluded that cyclophilin released in the host cell cytosol by T. cruzi mediates the increase of ROS, required to boost parasite proliferation in mammalian hosts.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trypanosoma cruzi / Espécies Reativas de Oxigênio / Ciclofilinas / Citosol / Interações Hospedeiro-Parasita Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trypanosoma cruzi / Espécies Reativas de Oxigênio / Ciclofilinas / Citosol / Interações Hospedeiro-Parasita Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article