Cyclophilin 19 secreted in the host cell cytosol by Trypanosoma cruzi promotes ROS production required for parasite growth

Autor(es)

dos Santos, Gregory Pedroso ^[1] ; Abukawa, Fernanda Midori ^[1] ; Souza-Melo, Normanda ^[1] ; Alcantara, Laura Maria ^[1] ; Bittencourt-Cunha, Paula ^[1] ; Moraes, Carolina Borsoi ^[2] ; Jha, Bijay Kumar ^[3] ; McGwire, Bradford S. ^[3] ; Moretti, Nilmar Silvio ^[1] ; Schenkman, Sergio ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, R Pedro de Toledo 669 L6A, BR-04039032 Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Dept Ciencias Farmaceut, Diadema, SP - Brazil

^[3] Ohio State Univ, Dept Internal Med, Div Infect Dis, Columbus, OH 43210 - USA

• Tipo de documento: Artigo Científico
• Fonte: Cellular Microbiology; v. 23, n. 4 DEC 2020.
• Citações Web of Science: 0

Resumo

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 p47(phox), as observed to the endogenous cyclophilin A, suggesting some mechanisms involved with the translocation process of the regulatory subunit p47(phox) 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. (AU)

• Processo FAPESP: 18/09948-0 - Estudo da acetilação proteica em Leishmania
• Beneficiário: Nilmar Silvio Moretti
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/02416-0 - Secreção de proteínas em Trypanosoma
• Beneficiário: Normanda Souza Melo
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/19303-4 - Efeito da ciclofilina 19 de Trypanosoma cruzi em células de mamífero
• Beneficiário: Fernanda Midori Abukawa
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 18/07766-2 - Caracterização da TcCyp19 e avaliação do seu papel durante a infecção celular por Trypanosoma cruzi
• Beneficiário: Gregory Pedroso dos Santos
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto