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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005714/ https://www.ncbi.nlm.nih.gov/pubmed/33791239 http://dx.doi.org/10.3389/fcimb.2021.631333 |
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author | Santos, Marina L. S. Coimbra, Roney S. Sousa, Tais N. Guimarães, Luiz F. F. Gomes, Matheus S. Amaral, Laurence R. Pereira, Dhelio B. Fontes, Cor J. F. Hawwari, Ibrahim Franklin, Bernardo S. Carvalho, Luzia H. |
author_facet | Santos, Marina L. S. Coimbra, Roney S. Sousa, Tais N. Guimarães, Luiz F. F. Gomes, Matheus S. Amaral, Laurence R. Pereira, Dhelio B. Fontes, Cor J. F. Hawwari, Ibrahim Franklin, Bernardo S. Carvalho, Luzia H. |
author_sort | Santos, Marina L. S. |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-8005714 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80057142021-03-30 The Interface Between Inflammatory Mediators and MicroRNAs in Plasmodium vivax Severe Thrombocytopenia Santos, Marina L. S. Coimbra, Roney S. Sousa, Tais N. Guimarães, Luiz F. F. Gomes, Matheus S. Amaral, Laurence R. Pereira, Dhelio B. Fontes, Cor J. F. Hawwari, Ibrahim Franklin, Bernardo S. Carvalho, Luzia H. Front Cell Infect Microbiol Cellular and Infection Microbiology 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. Frontiers Media S.A. 2021-03-15 /pmc/articles/PMC8005714/ /pubmed/33791239 http://dx.doi.org/10.3389/fcimb.2021.631333 Text en Copyright © 2021 Santos, Coimbra, Sousa, Guimarães, Gomes, Amaral, Pereira, Fontes, Hawwari, Franklin and Carvalho http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cellular and Infection Microbiology Santos, Marina L. S. Coimbra, Roney S. Sousa, Tais N. Guimarães, Luiz F. F. Gomes, Matheus S. Amaral, Laurence R. Pereira, Dhelio B. Fontes, Cor J. F. Hawwari, Ibrahim Franklin, Bernardo S. Carvalho, Luzia H. The Interface Between Inflammatory Mediators and MicroRNAs in Plasmodium vivax Severe Thrombocytopenia |
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 | Cellular and Infection Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005714/ https://www.ncbi.nlm.nih.gov/pubmed/33791239 http://dx.doi.org/10.3389/fcimb.2021.631333 |
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