The Interface Between Inflammatory Mediators and MicroRNAs in Plasmodium vivax Severe Thrombocytopenia

Frontiers in Cellular and Infection Microbiology

Dhelio B. Pereira¹  Cor J. F. Fontes²  Roney S. Coimbra³  Tais N. Sousa³  Luzia H. Carvalho³  Marina L. S. Santos³  Luiz F. F. Guimarães³  Laurence R. Amaral⁴  Matheus S. Gomes⁴  Ibrahim Hawwari⁵  Bernardo S. Franklin⁵ 

[1] Dep. Pesquisa Clínica e Medicina Translacional, Centro de Pesquisas em Medicina Tropical, Porto Velho, Brazil;Departamento de Clínica Médica, Universidade Federal de Mato Grosso, Cuiabá, Brazil;Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brazil;Laboratório de Bioinformática e Análises Moleculares, Rede Multidisciplinar de Pesquisa, Ciência e Tecnologia, Universidade Federal de Uberlândia, Patos de Minas, Brazil;Medical Faculty, Institute of Innate Immunity, University of Bonn, Bonn, Germany;

关键词: Plasmodium vivax;    malaria;    thrombocytopenia;    miRNA;    cytokine;    chemokine;   

DOI  :  10.3389/fcimb.2021.631333

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

CC BY