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https://www.arca.fiocruz.br/handle/icict/51152
THE INTERFACE BETWEEN INFLAMMATORY MEDIATORS AND MICRORNAS IN PLASMODIUM VIVAX SEVERE THROMBOCYTOPENIA
Author
Affilliation
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Universidade Federal de Uberlândia. Rede Multidisciplinar de Pesquisa, Ciência e Tecnologia. Laboratório de Bioinformática e Análises Moleculares. Patos de Minas, MG, Brazil.
Universidade Federal de Uberlândia. Rede Multidisciplinar de Pesquisa, Ciência e Tecnologia. Laboratório de Bioinformática e Análises Moleculares. Patos de Minas, MG, Brazil.
Centro de Pesquisas em Medicina Tropical. Departamento de Pesquisa Clínica e Medicina Translacional. Porto Velho, RO. Brazil.
Universidade Federal de Mato Grosso. Departamento de Clínica Médica. Cuiabá, MT, Brazil.
Medical Faculty. Institute of Innate Immunity. University of Bonn. Bonn, Germany.
Medical Faculty. Institute of Innate Immunity. University of Bonn. Bonn, Germany.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Universidade Federal de Uberlândia. Rede Multidisciplinar de Pesquisa, Ciência e Tecnologia. Laboratório de Bioinformática e Análises Moleculares. Patos de Minas, MG, Brazil.
Universidade Federal de Uberlândia. Rede Multidisciplinar de Pesquisa, Ciência e Tecnologia. Laboratório de Bioinformática e Análises Moleculares. Patos de Minas, MG, Brazil.
Centro de Pesquisas em Medicina Tropical. Departamento de Pesquisa Clínica e Medicina Translacional. Porto Velho, RO. Brazil.
Universidade Federal de Mato Grosso. Departamento de Clínica Médica. Cuiabá, MT, Brazil.
Medical Faculty. Institute of Innate Immunity. University of Bonn. Bonn, Germany.
Medical Faculty. Institute of Innate Immunity. University of Bonn. Bonn, Germany.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Abstract
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-g 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.
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