Paracrine Signaling Mediated by the Cytosolic Tryparedoxin Peroxidase of <i>Trypanosoma cruzi</i>
Peroxiredoxins are abundant and ubiquitous proteins that participate in different cellular functions, such as oxidant detoxification, protein folding, and intracellular signaling. Under different cellular conditions, peroxiredoxins can be secreted by different parasites, promoting the induction of i...
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| Format: | Article |
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MDPI AG
2024-01-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/13/1/67 |
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| author | María Laura Chiribao Florencia Díaz-Viraqué María Gabriela Libisch Carlos Batthyány Narcisa Cunha Wanderley De Souza Adriana Parodi-Talice Carlos Robello |
| author_facet | María Laura Chiribao Florencia Díaz-Viraqué María Gabriela Libisch Carlos Batthyány Narcisa Cunha Wanderley De Souza Adriana Parodi-Talice Carlos Robello |
| author_sort | María Laura Chiribao |
| collection | DOAJ |
| description | Peroxiredoxins are abundant and ubiquitous proteins that participate in different cellular functions, such as oxidant detoxification, protein folding, and intracellular signaling. Under different cellular conditions, peroxiredoxins can be secreted by different parasites, promoting the induction of immune responses in hosts. In this work, we demonstrated that the cytosolic tryparedoxin peroxidase of <i>Trypanosoma cruzi</i> (cTXNPx) is secreted by epimastigotes and trypomastigotes associated with extracellular vesicles and also as a vesicle-free protein. By confocal microscopy, we show that cTXNPx can enter host cells by an active mechanism both through vesicles and as a recombinant protein. Transcriptomic analysis revealed that cTXNPx induces endoplasmic reticulum stress and interleukin-8 expression in epithelial cells. This analysis also suggested alterations in cholesterol metabolism in cTXNPx-treated cells, which was confirmed by immunofluorescence showing the accumulation of LDL and the induction of LDL receptors in both epithelial cells and macrophages. BrdU incorporation assays and qPCR showed that cTXNPx has a mitogenic, proliferative, and proinflammatory effect on these cells in a dose–dependent manner. Importantly, we also demonstrated that cTXNPx acts as a paracrine virulence factor, increasing the susceptibility to infection in cTXNPx-pretreated epithelial cells by approximately 40%. Although the results presented in this work are from in vitro studies and likely underestimate the complexity of parasite–host interactions, our work suggests a relevant role for this protein in establishing infection. |
| first_indexed | 2024-03-08T10:38:27Z |
| format | Article |
| id | doaj.art-770d127d64b049a6b00f6c5eaf032b5e |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-08T10:38:27Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-770d127d64b049a6b00f6c5eaf032b5e2024-01-26T18:03:47ZengMDPI AGPathogens2076-08172024-01-011316710.3390/pathogens13010067Paracrine Signaling Mediated by the Cytosolic Tryparedoxin Peroxidase of <i>Trypanosoma cruzi</i>María Laura Chiribao0Florencia Díaz-Viraqué1María Gabriela Libisch2Carlos Batthyány3Narcisa Cunha4Wanderley De Souza5Adriana Parodi-Talice6Carlos Robello7Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo 11000, UruguayLaboratorio de Interacciones Hospedero–Patógeno—UBM, Institut Pasteur Montevideo, Montevideo 11000, UruguayLaboratorio de Interacciones Hospedero–Patógeno—UBM, Institut Pasteur Montevideo, Montevideo 11000, UruguayLaboratory of Vascular Biology and Drug Development, Institut Pasteur Montevideo, Montevideo 11000, UruguayInstituto de Biofísica Carlos Chagas Filho, Centro Nacional de Biologia Estrutural e Bioimagem (CENABIO), Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-901, BrazilInstituto de Biofísica Carlos Chagas Filho, Centro Nacional de Biologia Estrutural e Bioimagem (CENABIO), Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-901, BrazilLaboratorio de Interacciones Hospedero–Patógeno—UBM, Institut Pasteur Montevideo, Montevideo 11000, UruguayDepartamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo 11000, UruguayPeroxiredoxins are abundant and ubiquitous proteins that participate in different cellular functions, such as oxidant detoxification, protein folding, and intracellular signaling. Under different cellular conditions, peroxiredoxins can be secreted by different parasites, promoting the induction of immune responses in hosts. In this work, we demonstrated that the cytosolic tryparedoxin peroxidase of <i>Trypanosoma cruzi</i> (cTXNPx) is secreted by epimastigotes and trypomastigotes associated with extracellular vesicles and also as a vesicle-free protein. By confocal microscopy, we show that cTXNPx can enter host cells by an active mechanism both through vesicles and as a recombinant protein. Transcriptomic analysis revealed that cTXNPx induces endoplasmic reticulum stress and interleukin-8 expression in epithelial cells. This analysis also suggested alterations in cholesterol metabolism in cTXNPx-treated cells, which was confirmed by immunofluorescence showing the accumulation of LDL and the induction of LDL receptors in both epithelial cells and macrophages. BrdU incorporation assays and qPCR showed that cTXNPx has a mitogenic, proliferative, and proinflammatory effect on these cells in a dose–dependent manner. Importantly, we also demonstrated that cTXNPx acts as a paracrine virulence factor, increasing the susceptibility to infection in cTXNPx-pretreated epithelial cells by approximately 40%. Although the results presented in this work are from in vitro studies and likely underestimate the complexity of parasite–host interactions, our work suggests a relevant role for this protein in establishing infection.https://www.mdpi.com/2076-0817/13/1/67peroxiredoxintryparedoxin peroxidaseChagas diseasesignaling<i>Trypanosoma cruzi</i> |
| spellingShingle | María Laura Chiribao Florencia Díaz-Viraqué María Gabriela Libisch Carlos Batthyány Narcisa Cunha Wanderley De Souza Adriana Parodi-Talice Carlos Robello Paracrine Signaling Mediated by the Cytosolic Tryparedoxin Peroxidase of <i>Trypanosoma cruzi</i> Pathogens peroxiredoxin tryparedoxin peroxidase Chagas disease signaling <i>Trypanosoma cruzi</i> |
| title | Paracrine Signaling Mediated by the Cytosolic Tryparedoxin Peroxidase of <i>Trypanosoma cruzi</i> |
| title_full | Paracrine Signaling Mediated by the Cytosolic Tryparedoxin Peroxidase of <i>Trypanosoma cruzi</i> |
| title_fullStr | Paracrine Signaling Mediated by the Cytosolic Tryparedoxin Peroxidase of <i>Trypanosoma cruzi</i> |
| title_full_unstemmed | Paracrine Signaling Mediated by the Cytosolic Tryparedoxin Peroxidase of <i>Trypanosoma cruzi</i> |
| title_short | Paracrine Signaling Mediated by the Cytosolic Tryparedoxin Peroxidase of <i>Trypanosoma cruzi</i> |
| title_sort | paracrine signaling mediated by the cytosolic tryparedoxin peroxidase of i trypanosoma cruzi i |
| topic | peroxiredoxin tryparedoxin peroxidase Chagas disease signaling <i>Trypanosoma cruzi</i> |
| url | https://www.mdpi.com/2076-0817/13/1/67 |
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