The Interface Between Inflammatory Mediators and MicroRNAs in Plasmodium vivax Severe Thrombocytopenia
Severe thrombocytopenia can be a determinant factor in the morbidity of Plasmodium vivax, the most widespread human malaria parasite. Although immune mechanisms may drive P. vivax-induced severe thrombocytopenia (PvST), the current data on the cytokine landscape in PvST is scarce and often conflicti...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-03-01
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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.2021.631333/full |
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| author | Marina L. S. Santos Roney S. Coimbra Tais N. Sousa Luiz F. F. Guimarães Matheus S. Gomes Laurence R. Amaral Dhelio B. Pereira Cor J. F. Fontes Ibrahim Hawwari Bernardo S. Franklin Luzia H. Carvalho |
| author_facet | Marina L. S. Santos Roney S. Coimbra Tais N. Sousa Luiz F. F. Guimarães Matheus S. Gomes Laurence R. Amaral Dhelio B. Pereira Cor J. F. Fontes Ibrahim Hawwari Bernardo S. Franklin Luzia H. Carvalho |
| author_sort | Marina L. S. Santos |
| collection | DOAJ |
| description | Severe thrombocytopenia can be a determinant factor in the morbidity of Plasmodium vivax, the most widespread human malaria parasite. Although immune mechanisms may drive P. vivax-induced severe thrombocytopenia (PvST), the current data on the cytokine landscape in PvST is scarce and often conflicting. Here, we hypothesized that the analysis of the bidirectional circuit of inflammatory mediators and their regulatory miRNAs would lead to a better understanding of the mechanisms underlying PvST. For that, we combined Luminex proteomics, NanoString miRNA quantification, and machine learning to evaluate an extensive array of plasma mediators in uncomplicated P. vivax patients with different degrees of thrombocytopenia. Unsupervised clustering analysis identified a set of PvST-linked inflammatory (CXCL10, CCL4, and IL-18) and regulatory (IL-10, IL-1Ra, HGF) mediators. Among the mediators associated with PvST, IL-6 and IL-8 were critical to discriminate P. vivax subgroups, while CCL2 and IFN-γ from healthy controls. Supervised machine learning spotlighted IL-10 in P. vivax-mediated thrombocytopenia and provided evidence for a potential signaling route involving IL-8 and HGF. Finally, we identified a set of miRNAs capable of modulating these signaling pathways. In conclusion, the results place IL-10 and IL-8/HGF in the center of PvST and propose investigating these signaling pathways across the spectrum of malaria infections. |
| first_indexed | 2024-12-22T16:21:00Z |
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| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-22T16:21:00Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-bfbca1e9cc3f4254a142ebdfb6b55c0b2022-12-21T18:20:14ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882021-03-011110.3389/fcimb.2021.631333631333The Interface Between Inflammatory Mediators and MicroRNAs in Plasmodium vivax Severe ThrombocytopeniaMarina L. S. Santos0Roney S. Coimbra1Tais N. Sousa2Luiz F. F. Guimarães3Matheus S. Gomes4Laurence R. Amaral5Dhelio B. Pereira6Cor J. F. Fontes7Ibrahim Hawwari8Bernardo S. Franklin9Luzia H. Carvalho10Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, BrazilInstituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, BrazilInstituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, BrazilInstituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, BrazilLaboratório de Bioinformática e Análises Moleculares, Rede Multidisciplinar de Pesquisa, Ciência e Tecnologia, Universidade Federal de Uberlândia, Patos de Minas, BrazilLaboratório de Bioinformática e Análises Moleculares, Rede Multidisciplinar de Pesquisa, Ciência e Tecnologia, Universidade Federal de Uberlândia, Patos de Minas, BrazilDep. Pesquisa Clínica e Medicina Translacional, Centro de Pesquisas em Medicina Tropical, Porto Velho, BrazilDepartamento de Clínica Médica, Universidade Federal de Mato Grosso, Cuiabá, BrazilMedical Faculty, Institute of Innate Immunity, University of Bonn, Bonn, GermanyMedical Faculty, Institute of Innate Immunity, University of Bonn, Bonn, GermanyInstituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, BrazilSevere thrombocytopenia can be a determinant factor in the morbidity of Plasmodium vivax, the most widespread human malaria parasite. Although immune mechanisms may drive P. vivax-induced severe thrombocytopenia (PvST), the current data on the cytokine landscape in PvST is scarce and often conflicting. Here, we hypothesized that the analysis of the bidirectional circuit of inflammatory mediators and their regulatory miRNAs would lead to a better understanding of the mechanisms underlying PvST. For that, we combined Luminex proteomics, NanoString miRNA quantification, and machine learning to evaluate an extensive array of plasma mediators in uncomplicated P. vivax patients with different degrees of thrombocytopenia. Unsupervised clustering analysis identified a set of PvST-linked inflammatory (CXCL10, CCL4, and IL-18) and regulatory (IL-10, IL-1Ra, HGF) mediators. Among the mediators associated with PvST, IL-6 and IL-8 were critical to discriminate P. vivax subgroups, while CCL2 and IFN-γ from healthy controls. Supervised machine learning spotlighted IL-10 in P. vivax-mediated thrombocytopenia and provided evidence for a potential signaling route involving IL-8 and HGF. Finally, we identified a set of miRNAs capable of modulating these signaling pathways. In conclusion, the results place IL-10 and IL-8/HGF in the center of PvST and propose investigating these signaling pathways across the spectrum of malaria infections.https://www.frontiersin.org/articles/10.3389/fcimb.2021.631333/fullPlasmodium vivaxmalariathrombocytopeniamiRNAcytokinechemokine |
| spellingShingle | Marina L. S. Santos Roney S. Coimbra Tais N. Sousa Luiz F. F. Guimarães Matheus S. Gomes Laurence R. Amaral Dhelio B. Pereira Cor J. F. Fontes Ibrahim Hawwari Bernardo S. Franklin Luzia H. Carvalho The Interface Between Inflammatory Mediators and MicroRNAs in Plasmodium vivax Severe Thrombocytopenia Frontiers in Cellular and Infection Microbiology Plasmodium vivax malaria thrombocytopenia miRNA cytokine chemokine |
| title | The Interface Between Inflammatory Mediators and MicroRNAs in Plasmodium vivax Severe Thrombocytopenia |
| title_full | The Interface Between Inflammatory Mediators and MicroRNAs in Plasmodium vivax Severe Thrombocytopenia |
| title_fullStr | The Interface Between Inflammatory Mediators and MicroRNAs in Plasmodium vivax Severe Thrombocytopenia |
| title_full_unstemmed | The Interface Between Inflammatory Mediators and MicroRNAs in Plasmodium vivax Severe Thrombocytopenia |
| title_short | The Interface Between Inflammatory Mediators and MicroRNAs in Plasmodium vivax Severe Thrombocytopenia |
| title_sort | interface between inflammatory mediators and micrornas in plasmodium vivax severe thrombocytopenia |
| topic | Plasmodium vivax malaria thrombocytopenia miRNA cytokine chemokine |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2021.631333/full |
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