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• W2552231036 endingPage "e0005123" @default.
• W2552231036 startingPage "e0005123" @default.
• W2552231036 abstract "Visceral leishmaniasis (VL) can be lethal if untreated; however, the majority of human infections with the etiological agents are asymptomatic. Using Illumina Bead Chip microarray technology, we investigated the patterns of gene expression in blood of active VL patients, asymptomatic infected individuals, patients under remission of VL and controls. Computational analyses based on differential gene expression, gene set enrichment, weighted gene co-expression networks and cell deconvolution generated data demonstrating discriminative transcriptional signatures. VL patients exhibited transcriptional profiles associated with pathways and gene modules reflecting activation of T lymphocytes via MHC class I and type I interferon signaling, as well as an overall down regulation of pathways and gene modules related to myeloid cells, mainly due to differences in the relative proportions of monocytes and neutrophils. Patients under remission of VL presented heterogeneous transcriptional profiles associated with activation of T lymphocytes via MHC class I, type I interferon signaling and cell cycle and, importantly, transcriptional activity correlated with activation of Notch signaling pathway and gene modules that reflected increased proportions of B cells after treatment of disease. Asymptomatic and uninfected individuals presented similar gene expression profiles, nevertheless, asymptomatic individuals exhibited particularities which suggest an efficient regulation of lymphocyte activation and a strong association with a type I interferon response. Of note, we validated a set of target genes by RT-qPCR and demonstrate the robustness of expression data acquired by microarray analysis. In conclusion, this study profiles the immune response during distinct states of infection of humans with Leishmania infantum with a novel strategy that indicates the molecular pathways that contribute to the progression of the disease, while also providing insights into transcriptional activity that can drive protective mechanisms." @default.
• W2552231036 created "2016-11-30" @default.
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• W2552231036 date "2016-11-09" @default.
• W2552231036 modified "2023-09-23" @default.
• W2552231036 title "Blood Transcriptional Profiling Reveals Immunological Signatures of Distinct States of Infection of Humans with Leishmania infantum" @default.
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• W2552231036 doi "https://doi.org/10.1371/journal.pntd.0005123" @default.
• W2552231036 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5102635" @default.
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• W2552231036 hasPublicationYear "2016" @default.
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