RESUMO
Leprosy presents as a clinical and immunological spectrum of disease. With the use of gene expression profiling, we observed that a distinction in gene expression correlates with and accurately classifies the clinical form of the disease. Genes belonging to the leukocyte immunoglobulin-like receptor (LIR) family were significantly up-regulated in lesions of lepromatous patients suffering from the disseminated form of the infection. In functional studies, LIR-7 suppressed innate host defense mechanisms by shifting monocyte production from interleukin-12 toward interleukin-10 and by blocking antimicrobial activity triggered by Toll-like receptors. Gene expression profiles may be useful in defining clinical forms of disease and providing insights into the regulation of immune responses to pathogens.
Assuntos
Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Hanseníase Virchowiana/classificação , Hanseníase Virchowiana/genética , Hanseníase Tuberculoide/classificação , Hanseníase Tuberculoide/genética , Algoritmos , Análise por Conglomerados , Contagem de Colônia Microbiana , Citocinas/genética , Citocinas/metabolismo , Genes de Imunoglobulinas , Humanos , Imunidade Celular , Imunidade Inata , Hanseníase Virchowiana/imunologia , Hanseníase Virchowiana/fisiopatologia , Hanseníase Tuberculoide/imunologia , Hanseníase Tuberculoide/fisiopatologia , Macrófagos Alveolares/microbiologia , Glicoproteínas de Membrana/imunologia , Mycobacterium tuberculosis/crescimento & desenvolvimento , Mycobacterium tuberculosis/imunologia , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , Análise de Componente Principal , Receptores de Superfície Celular/imunologia , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Receptores Toll-Like , Regulação para CimaRESUMO
Leprosy presents as a clinical and immunological spectrum of disease. With the use of gene expression profiling, we observed that a distinction in gene expression correlates with and accurately classifies the clinical form of the disease. Genes belonging to the leukocyte immunoglobulin-like receptor (LIR) family were significantly up-regulated in lesions of lepromatous patients suffering from the disseminated form of the infection. In functional studies, LIR-7 suppressed innate host defense mechanisms by shifting monocyte production from interleukin-12 toward interleukin-10 and by blocking antimicrobial activity triggered by Toll-like receptors. Gene expression profiles may be useful in defining clinical forms of disease and providing insights into the regulation of immune responses to pathogens.