miR-548d-3p Alters Parasite Growth and Inflammation in Leishmania (Viannia) braziliensis Infection
American Tegumentary Leishmaniasis (ATL) is an endemic disease in Latin America, mainly caused in Brazil by Leishmania (Viannia) braziliensis. Clinical manifestations vary from mild, localized cutaneous leishmaniasis (CL) to aggressive mucosal disease. The host immune response strongly determines th...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2021.687647/full |
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| author | Marina de Assis Souza Eduardo Milton Ramos-Sanchez Eduardo Milton Ramos-Sanchez Sandra Márcia Muxel Dimitris Lagos Luiza Campos Reis Valéria Rêgo Alves Pereira Maria Edileuza Felinto Brito Ricardo Andrade Zampieri Paul Martin Kaye Lucile Maria Floeter-Winter Hiro Goto Hiro Goto |
| author_facet | Marina de Assis Souza Eduardo Milton Ramos-Sanchez Eduardo Milton Ramos-Sanchez Sandra Márcia Muxel Dimitris Lagos Luiza Campos Reis Valéria Rêgo Alves Pereira Maria Edileuza Felinto Brito Ricardo Andrade Zampieri Paul Martin Kaye Lucile Maria Floeter-Winter Hiro Goto Hiro Goto |
| author_sort | Marina de Assis Souza |
| collection | DOAJ |
| description | American Tegumentary Leishmaniasis (ATL) is an endemic disease in Latin America, mainly caused in Brazil by Leishmania (Viannia) braziliensis. Clinical manifestations vary from mild, localized cutaneous leishmaniasis (CL) to aggressive mucosal disease. The host immune response strongly determines the outcome of infection and pattern of disease. However, the pathogenesis of ATL is not well understood, and host microRNAs (miRNAs) may have a role in this context. In the present study, miRNAs were quantified using qPCR arrays in human monocytic THP-1 cells infected in vitro with L. (V.) braziliensis promastigotes and in plasma from patients with ATL, focusing on inflammatory response-specific miRNAs. Patients with active or self-healed cutaneous leishmaniasis patients, with confirmed parasitological or immunological diagnosis, were compared with healthy controls. Computational target prediction of significantly-altered miRNAs from in vitro L. (V.) braziliensis-infected THP-1 cells revealed predicted targets involved in diverse pathways, including chemokine signaling, inflammatory, cellular proliferation, and tissue repair processes. In plasma, we observed distinct miRNA expression in patients with self-healed and active lesions compared with healthy controls. Some miRNAs dysregulated during THP-1 in vitro infection were also found in plasma from self-healed patients, including miR-548d-3p, which was upregulated in infected THP-1 cells and in plasma from self-healed patients. As miR-548d-3p was predicted to target the chemokine pathway and inflammation is a central to the pathogenesis of ATL, we evaluated the effect of transient transfection of a miR-548d-3p inhibitor on L. (V.) braziliensis infected-THP-1 cells. Inhibition of miR-548d-3p reduced parasite growth early after infection and increased production of MCP1/CCL2, RANTES/CCL5, and IP10/CXCL10. In plasma of self-healed patients, MCP1/CCL2, RANTES/CCL5, and IL-8/CXCL8 concentrations were significantly decreased and MIG/CXCL9 and IP-10/CXCL10 increased compared to patients with active disease. These data suggest that by modulating miRNAs, L. (V.) braziliensis may interfere with chemokine production and hence the inflammatory processes underpinning lesion resolution. Our data suggest miR-548d-3p could be further evaluated as a prognostic marker for ATL and/or as a host-directed therapeutic target. |
| first_indexed | 2024-12-21T19:32:05Z |
| format | Article |
| id | doaj.art-621225ee3ac542869143f62e25723750 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-21T19:32:05Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-621225ee3ac542869143f62e257237502022-12-21T18:52:41ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882021-06-011110.3389/fcimb.2021.687647687647miR-548d-3p Alters Parasite Growth and Inflammation in Leishmania (Viannia) braziliensis InfectionMarina de Assis Souza0Eduardo Milton Ramos-Sanchez1Eduardo Milton Ramos-Sanchez2Sandra Márcia Muxel3Dimitris Lagos4Luiza Campos Reis5Valéria Rêgo Alves Pereira6Maria Edileuza Felinto Brito7Ricardo Andrade Zampieri8Paul Martin Kaye9Lucile Maria Floeter-Winter10Hiro Goto11Hiro Goto12Instituto de Medicina Tropical, Faculdade de Medicina, Universidade de São Paulo (IMTSP/USP), São Paulo, BrazilInstituto de Medicina Tropical, Faculdade de Medicina, Universidade de São Paulo (IMTSP/USP), São Paulo, BrazilDepartamento de Salud Publica, Facultad de Ciencias de La Salud, Universidad Nacional Toribio Rodriguez de Mendoza de Amazonas, Chachapoyas, PeruInstituto de Biociências, Universidade de São Paulo, São Paulo, BrazilYork Biomedical Research Institute, Hull York Medical School, University of York, York, United KingdomInstituto de Medicina Tropical, Faculdade de Medicina, Universidade de São Paulo (IMTSP/USP), São Paulo, BrazilInstituto Aggeu Magalhães, Fundação Oswaldo Cruz (IAM/FIOCRUZ), Recife, BrazilInstituto Aggeu Magalhães, Fundação Oswaldo Cruz (IAM/FIOCRUZ), Recife, BrazilInstituto de Biociências, Universidade de São Paulo, São Paulo, BrazilYork Biomedical Research Institute, Hull York Medical School, University of York, York, United KingdomInstituto de Biociências, Universidade de São Paulo, São Paulo, BrazilInstituto de Medicina Tropical, Faculdade de Medicina, Universidade de São Paulo (IMTSP/USP), São Paulo, BrazilDepartamento de Medicina Preventiva, Faculdade de Medicina, Universidade de São Paulo, São Paulo, BrazilAmerican Tegumentary Leishmaniasis (ATL) is an endemic disease in Latin America, mainly caused in Brazil by Leishmania (Viannia) braziliensis. Clinical manifestations vary from mild, localized cutaneous leishmaniasis (CL) to aggressive mucosal disease. The host immune response strongly determines the outcome of infection and pattern of disease. However, the pathogenesis of ATL is not well understood, and host microRNAs (miRNAs) may have a role in this context. In the present study, miRNAs were quantified using qPCR arrays in human monocytic THP-1 cells infected in vitro with L. (V.) braziliensis promastigotes and in plasma from patients with ATL, focusing on inflammatory response-specific miRNAs. Patients with active or self-healed cutaneous leishmaniasis patients, with confirmed parasitological or immunological diagnosis, were compared with healthy controls. Computational target prediction of significantly-altered miRNAs from in vitro L. (V.) braziliensis-infected THP-1 cells revealed predicted targets involved in diverse pathways, including chemokine signaling, inflammatory, cellular proliferation, and tissue repair processes. In plasma, we observed distinct miRNA expression in patients with self-healed and active lesions compared with healthy controls. Some miRNAs dysregulated during THP-1 in vitro infection were also found in plasma from self-healed patients, including miR-548d-3p, which was upregulated in infected THP-1 cells and in plasma from self-healed patients. As miR-548d-3p was predicted to target the chemokine pathway and inflammation is a central to the pathogenesis of ATL, we evaluated the effect of transient transfection of a miR-548d-3p inhibitor on L. (V.) braziliensis infected-THP-1 cells. Inhibition of miR-548d-3p reduced parasite growth early after infection and increased production of MCP1/CCL2, RANTES/CCL5, and IP10/CXCL10. In plasma of self-healed patients, MCP1/CCL2, RANTES/CCL5, and IL-8/CXCL8 concentrations were significantly decreased and MIG/CXCL9 and IP-10/CXCL10 increased compared to patients with active disease. These data suggest that by modulating miRNAs, L. (V.) braziliensis may interfere with chemokine production and hence the inflammatory processes underpinning lesion resolution. Our data suggest miR-548d-3p could be further evaluated as a prognostic marker for ATL and/or as a host-directed therapeutic target.https://www.frontiersin.org/articles/10.3389/fcimb.2021.687647/fullLeishmania braziliensismicroRNApathogenesisactive cutaneous leishmaniasisself-healed cutaneous leishmaniasisTHP-1 cells |
| spellingShingle | Marina de Assis Souza Eduardo Milton Ramos-Sanchez Eduardo Milton Ramos-Sanchez Sandra Márcia Muxel Dimitris Lagos Luiza Campos Reis Valéria Rêgo Alves Pereira Maria Edileuza Felinto Brito Ricardo Andrade Zampieri Paul Martin Kaye Lucile Maria Floeter-Winter Hiro Goto Hiro Goto miR-548d-3p Alters Parasite Growth and Inflammation in Leishmania (Viannia) braziliensis Infection Frontiers in Cellular and Infection Microbiology Leishmania braziliensis microRNA pathogenesis active cutaneous leishmaniasis self-healed cutaneous leishmaniasis THP-1 cells |
| title | miR-548d-3p Alters Parasite Growth and Inflammation in Leishmania (Viannia) braziliensis Infection |
| title_full | miR-548d-3p Alters Parasite Growth and Inflammation in Leishmania (Viannia) braziliensis Infection |
| title_fullStr | miR-548d-3p Alters Parasite Growth and Inflammation in Leishmania (Viannia) braziliensis Infection |
| title_full_unstemmed | miR-548d-3p Alters Parasite Growth and Inflammation in Leishmania (Viannia) braziliensis Infection |
| title_short | miR-548d-3p Alters Parasite Growth and Inflammation in Leishmania (Viannia) braziliensis Infection |
| title_sort | mir 548d 3p alters parasite growth and inflammation in leishmania viannia braziliensis infection |
| topic | Leishmania braziliensis microRNA pathogenesis active cutaneous leishmaniasis self-healed cutaneous leishmaniasis THP-1 cells |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2021.687647/full |
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