Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/11741
Title: Gene Expression Profiling Specifies Chemokine, Mitochondrial and Lipid Metabolism Signatures in Leprosy
Authors: Guerreiro, Luana Tatiana Albuquerque
Ferreira, Anna Beatriz Robottom
Alves, Marcelo Ribeiro
Pinto, Thiago Gomes Toledo
Brito, Tiana Rosa
Rosa, Patrícia Sammarco
Sandoval, Felipe Galvan
Jardim, Márcia Rodrigues
Antunes, Sérgio Gomes
Shannon, Edward J.
Sarno, Euzenir Nunes
Pessolani, Maria Cristina Vidal
Williams, Diana Lynn
Moraes, Milton Ozório
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Pesquisa em Farmacogenética. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Instituto Lauro de Souza Lima. Bauru, SP, Brasil.
Louisiana State University. School of Veterinary Medicine. Laboratory Research Branch. Division of National Hansen’s Disease Programs. Bureau of Primary Health Care (BPHC). Health Resources and Services Administration (HRSA). Baton Rouge, Louisiana, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Louisiana State University. School of Veterinary Medicine. Laboratory Research Branch. Division of National Hansen’s Disease Programs. Bureau of Primary Health Care (BPHC). Health Resources and Services Administration (HRSA). Baton Rouge, Louisiana, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.
Louisiana State University. School of Veterinary Medicine. Laboratory Research Branch. Division of National Hansen’s Disease Programs. Bureau of Primary Health Care (BPHC). Health Resources and Services Administration (HRSA). Baton Rouge, Louisiana, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Abstract: Herein, we performed microarray experiments in Schwann cells infected with live M. leprae and identified novel differentially expressed genes (DEG) in M. leprae infected cells. Also, we selected candidate genes associated or implicated with leprosy in genetic studies and biological experiments. Forty-seven genes were selected for validation in two independent types of samples by multiplex qPCR. First, an in vitro model using THP-1 cells was infected with live Mycobacterium leprae and M. bovis bacillus Calmette-Gue´rin (BCG). In a second situation, mRNA obtained from nerve biopsies from patients with leprosy or other peripheral neuropathies was tested. We detected DEGs that discriminate M. bovis BCG from M. leprae infection. Specific signatures of susceptible responses after M. leprae infection when compared to BCG lead to repression of genes, including CCL2, CCL3, IL8 and SOD2. The same 47-gene set was screened in nerve biopsies, which corroborated the downregulation of CCL2 and CCL3 in leprosy, but also evidenced the down-regulation of genes involved in mitochondrial metabolism, and the up-regulation of genes involved in lipid metabolism and ubiquitination. Finally, a gene expression signature from DEG was identified in patients confirmed of having leprosy. A classification tree was able to ascertain 80% of the cases as leprosy or non-leprous peripheral neuropathy based on the expression of only LDLR and CCL4. A general immune and mitochondrial hypo-responsive state occurs in response to M. leprae infection. Also, the most important genes and pathways have been highlighted providing new tools for early diagnosis and treatment of leprosy.
Keywords: Leprosy
Lipid Metabolism
Chemokine
Mitochondrial
Genes
DeCS: Hanseníase
Quimiocinas
Mitocôndrias
Metabolismo Lipídico
Genes
Issue Date: 2013
Publisher: Plos One
Citation: GUERREIRO, Luana Tatiana Albuquerque. Gene Expression Profiling Specifies Chemokine, Mitochondrial and Lipid Metabolism Signatures in Leprosy. Plos One, v.8, n.6, 11p, 2013.
DOI: 10.1371/journal.pone.0064748
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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