biostudies-literatureAssis PAFundação de Amparo de Pesquisa do Estado de São PauloUS NIHNIAID NIH HHSFundação de Pesquisa do Estado de Minas GeraisBrazilian National Institute of Science and Technology for VaccinesNINDS NIH HHS1183-1197https://www.ebi.ac.uk/biostudies/studies/S-EPMC11215656biostudies-literatureUnknown108(4)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.Journal of leukocyte biologyIntegrative analysis of microRNA and mRNA expression profiles of monocyte-derived dendritic cells differentiation during experimental cerebral malaria.PMC11215656R01 NS098747U19AI089681R01NS098747R21AI131632R01AI079293465293/2014-0R21 AI131632U19 AI0896812016/23618-8R01 AI079293Fernandes Durso DGolenbock DTZaniratto RAssis PACunha-Neto ERodrigues Pinto Ferreira LTostes Gazzinelli RCarvalho-Silva ACChacon Cavalcante FfalseIntegrative analysis of microRNA and mRNA expression profiles of monocyte-derived dendritic cells differentiation during experimental cerebral malaria.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.2020-01-01T00:00:00Z2020 Oct2025-04-18T15:28:43.388Z2025-04-07T02:10:41.857ZS-EPMC112156563236202210.1002/jlb.1ma0320-731r10.1002/JLB.1MA0320-731R