Integrative analysis of microRNA and mRNA expression profiles of monocyte-derived dendritic cells differentiation during experimental cerebral malaria.

Autor: Assis PA; Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA., Fernandes Durso D; Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA., Chacon Cavalcante F; Laboratory of Immunopathology, Fundação Oswaldo Cruz - Minas, Belo Horizonte, Minas Gerais, Brazil., Zaniratto R; Laboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil., Carvalho-Silva AC; RNA Systems Biology Laboratory (RSBL), Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Cunha-Neto E; Laboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil.; Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine, São Paulo, Brazil., Golenbock DT; Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA., Rodrigues Pinto Ferreira L; RNA Systems Biology Laboratory (RSBL), Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Tostes Gazzinelli R; Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.; Laboratory of Immunopathology, Fundação Oswaldo Cruz - Minas, Belo Horizonte, Minas Gerais, Brazil.; Plataforma de Medicina Translacional, Fundação Oswaldo Cruz/Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Journal of leukocyte biology [J Leukoc Biol] 2020 Oct; Vol. 108 (4), pp. 1183-1197. Date of Electronic Publication: 2020 May 03.
DOI: 10.1002/JLB.1MA0320-731R
Abstrakt: Heterogeneity and high plasticity are common features of cells from the mononuclear phagocyte system: monocytes (MOs), macrophages, and dendritic cells (DCs). Upon activation by microbial agents, MO can differentiate into MO-derived DCs (MODCs). In previous work, we have shown that during acute infection with Plasmodium berghei ANKA (PbA), MODCs become, transiently, the main CD11b + myeloid population in the spleen (SP) and once recruited to the brain play an important role in the development of experimental cerebral malaria (ECM). Here, we isolated 4 cell populations: bone marrow (BM) MOs (BM-MOs) and SP-MOs from uninfected mice; BM inflammatory MOs (BM-iMOs) and SP-MODCs from PbA-infected mice and used a system biology approach to a holistic transcriptomic comparison and provide an interactome analysis by integrating differentially expressed miRNAs (DEMs) and their differentially expressed gene targets (DEGs) data. The Jaccard index (JI) was used for gauging the similarity and diversity among these cell populations. Whereas BM-MOs, BM-iMOs, and SP-MOs presented high similarity of DEGs, SP-MODCs distinguished by showing a greater number of DEGs. Moreover, functional analysis identified an enrichment in canonical pathways, such as DC maturation, neuroinflammation, and IFN signaling. Upstream regulator analysis identified IFNγ as the potential upstream molecule that can explain the observed DEMs-Target DEGs intersections in SP-MODCs. Finally, directed target analysis and in vivo/ex vivo assays indicate that SP-MODCs differentiate in the SP and IFNγ is a main driver of this process.
(©2020 Society for Leukocyte Biology.)
Databáze: MEDLINE
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