Author | Christensen, Stephen M | |
Author | Dillon, Laura A L | |
Author | Carvalho, Lucas Pedreira de | |
Author | Passos, Sara Timoteo | |
Author | Novais, Fernanda Oliveira | |
Author | Hughitt, V Keith | |
Author | Beiting, Daniel P | |
Author | Carvalho Filho, Edgar Marcelino | |
Author | Scott, Phillip | |
Author | El-Sayed, Najib M | |
Author | Mosser, David M | |
Access date | 2017-04-11T13:21:02Z | |
Available date | 2017-04-11T13:21:02Z | |
Document date | 2016 | |
Citation | CHRISTENSEN, S. M. et al. Meta-transcriptome Profiling of the Human-Leishmania braziliensis Cutaneous Lesion. PLoS Neglected Tropical Diseases, v. 10, n. 9, p. e0004992, 2016. | pt_BR |
ISSN | 1935-2727 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/18368 | |
Description | Carvalho Filho, E. M. Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.
“Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”. | pt_BR |
Sponsorship | National Institutes of Health NIAID (AI094773) and NIGMS (GM102589), and na International Collaboration for Infectious Disease Research (ICIDR) grant (U01-AUI088650). | pt_BR |
Language | eng | pt_BR |
Publisher | Public Library of Science | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Leishmania braziliensis | pt_BR |
Subject in Portuguese | Leishmaniose cutânea | pt_BR |
Subject in Portuguese | Pele | pt_BR |
Subject in Portuguese | Humano | pt_BR |
Subject in Portuguese | Biópsia | pt_BR |
Subject in Portuguese | DNA | pt_BR |
Subject in Portuguese | Infecção | pt_BR |
Title | Meta-transcriptome Profiling of the Human-Leishmania braziliensis Cutaneous Lesion | pt_BR |
Type | Article | pt_BR |
DOI | 10.1371/journal.pntd.0004992 | |
Abstract | Host and parasite gene expression in skin biopsies from Leishmania braziliensis-infected patients were simultaneously analyzed using high throughput RNA-sequencing. Biopsies were taken from 8 patients with early cutaneous leishmaniasis and 17 patients with late cutaneous leishmaniasis. Although parasite DNA was found in all patient lesions at the time of biopsy, the patients could be stratified into two groups: one lacking detectable parasite transcripts (PTNeg) in lesions, and another in which parasite transcripts were readily detected (PTPos). These groups exhibited substantial differences in host responses to infection. PTPos biopsies contained an unexpected increase in B lymphocyte-specific and immunoglobulin transcripts in the lesions, and an upregulation of immune inhibitory molecules. Biopsies without detectable parasite transcripts showed decreased evidence for B cell activation, but increased expression of antimicrobial genes and genes encoding skin barrier functions. The composition and abundance of L. braziliensis transcripts in PTPos lesions were surprisingly conserved among all six patients, with minimal meaningful differences between lesions from patients with early and late cutaneous leishmaniasis. The most abundant parasite transcripts expressed in lesions were distinct from transcripts expressed in vitro in human macrophage cultures infected with L. amazonensis or L. major. Therefore in vitro gene expression in macrophage monolayers may not be a strong predictor of gene expression in lesions. Some of the most highly expressed in vivo transcripts encoded amastin-like proteins, hypothetical genes, putative parasite virulence factors, as well as histones and tubulin. In summary, RNA sequencing allowed us to simultaneously analyze human and L. braziliensis transcriptomes in lesions of infected patients, and identify unexpected differences in host immune responses which correlated with active transcription of parasite genes. | pt_BR |
Affilliation | University of Maryland. Department of Cell Biology and Molecular Genetics. Maryland, USA | pt_BR |
Affilliation | University of Maryland. Department of Cell Biology and Molecular Genetics. Maryland, USA / University of Maryland. Center for Bioinformatics and Computational Biology. Maryland, USA | pt_BR |
Affilliation | Universidade Federal da Bahia. Salvador, BA, Brasil | pt_BR |
Affilliation | Universidade Federal da Bahia. Salvador, BA, Brasil | pt_BR |
Affilliation | The University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA | pt_BR |
Affilliation | University of Maryland. Department of Cell Biology and Molecular Genetics. Maryland, USA / University of Maryland. Center for Bioinformatics and Computational Biology. Maryland, USA | pt_BR |
Affilliation | The University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA | pt_BR |
Affilliation | Universidade Federal da Bahia. Salvador, BA, Brasil | pt_BR |
Affilliation | The University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA | pt_BR |
Affilliation | University of Maryland. Department of Cell Biology and Molecular Genetics. Maryland, USA / University of Maryland. Center for Bioinformatics and Computational Biology. Maryland, USA | pt_BR |
Affilliation | University of Maryland. Department of Cell Biology and Molecular Genetics. Maryland, USA | pt_BR |
Subject | Leishmania braziliensis | pt_BR |
Subject | Leishmaniose cutânea | pt_BR |
Subject | Skin | pt_BR |
Subject | Humans | pt_BR |
Subject | Biopsies | pt_BR |
Subject | DNA | pt_BR |
Subject | Infection | pt_BR |