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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Blood Transcriptional Profiling Reveals Immunological Signatures of Distinct States of Infection of Humans with Leishmania infantum

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Gardinassi, Luiz Gustavo ; Garcia, Gustavo Rocha ; Nery Costa, Carlos Henrique ; Silva, Vladimir Costa ; Ferreira de Miranda Santos, Isabel Kinney
Total Authors: 5
Document type: Journal article
Source: PLoS Neglected Tropical Diseases; v. 10, n. 11 NOV 2016.
Web of Science Citations: 8

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. (AU)

Grantee:Gustavo Rocha Garcia
Support Opportunities: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 11/23819-0 - Peripheral blood transcriptome and the characterization of chemical-structural and functional properties of immunoglobulin G in different clinical outcomes related to infection with Leishmania infantum chagasi
Grantee:Luiz Gustavo Araujo Gardinassi
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 14/25856-8 - The Role of IgG Fc N-Glycosylation on the Pathogenesis of Visceral Leishmaniasis: Insights Into New Strategies of Therapy
Grantee:Luiz Gustavo Araujo Gardinassi
Support Opportunities: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 12/06708-2 - RNA-Seq of bovine preipheral blood leukocytes: functional analysis of the transcriptome obtained after immunization with recombinant antigens from the cattle tick, Rhipicephalus microplus, and after infestations and validation of results with PCR arrays
Grantee:Isabel Kinney Ferreira de Miranda Santos
Support Opportunities: Regular Research Grants