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

Autor(es)

Gardinassi, Luiz Gustavo ; Garcia, Gustavo Rocha ; Nery Costa, Carlos Henrique ; Silva, Vladimir Costa ; Ferreira de Miranda Santos, Isabel Kinney

• Tipo de documento: Artigo Científico
• Fonte: PLoS Neglected Tropical Diseases; v. 10, n. 11 NOV 2016.
• Citações Web of Science: 8

Resumo

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)

• Processo FAPESP: 13/00382-0 - Prospecção do salivoma de carrapatos para descoberta de novos componentes antimicrobianos
• Beneficiário: Gustavo Rocha Garcia
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 11/23819-0 - O transcriptoma de sangue periférico e a caracterização de propriedades químico-estruturais e funcionais de imunoglobulina G em diferentes desfechos clínicos relacionados à infecção por Leishmania infantum chagasi
• Beneficiário: Luiz Gustavo Araujo Gardinassi
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/25856-8 - O Papel da N-glicosilação da Região Fc de IgG na Patogênese da Leishmaniose Visceral e a Avaliação de Novas Estratégias Terapêuticas
• Beneficiário: Luiz Gustavo Araujo Gardinassi
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 12/06708-2 - RNA-Seq de leucócitos de sangue periférico de bovinos: análise funcional do transcriptoma obtido frente à imunização com antígenos recombinantes do carrapato Rhipicephalus microplus e à infestação e validação dos resultados com arranjos de PCR
• Beneficiário: Isabel Kinney Ferreira de Miranda Santos
• Modalidade de apoio: Auxílio à Pesquisa - Regular