Caracterização do microtranscriptoma de macrófagos infectados por cepas saprófita, atenuada ou virulenta de Leptospira spp.
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Data
2018-10-26
Autores
Garcia, Leandro Encarnação [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
Leptospirose é considerada uma zoonose de importância global causada pela bactéria Leptospira spp. A incidência da doença chega a um milhão de casos severos no mundo, atingindo uma mortalidade de 60.000 óbitos/ano. Apesar de considerados avanços na pesquisa sobre a doença, há muito ainda a se descobrir sobre sua patogenicidade. A influência de mecanismos epigenéticos em processos patológicos, particularmente da regulação pós-transcricional mediada por RNAs não-codificadores, é fundamental. Uma gama de estudos vem relatando a influência desses mecanismos na resposta imune do hospedeiro em uma variedade de infecções bacterianas. O objetivo desse estudo foi identificar e caracterizar, pela primeira vez, a influência de miRNAs na regulação da resposta de macrófagos frente a infecção por Leptospira. Foi realizado um microtranscriptoma, através da técnica de microarranjo, em macrófafgos murinos J774A.1 desafiados por cepa virulenta, atenuada e saprófita de Leptospira após 8h de infecção. Após análise dos dados, identificamos 29 miRNAs modulados pela infecção comparados ao controle, com fold change ± 1.5 e p-valor<0,01. Na análise de enriquecimento funcional, encontramos um grande número de alvos para os miRNAs modulados participando em processos-chave da resposta imune. Podemos sugerir que a regulação pós-transcricional por miRNAs possui papel na resposta do hospedeiro em infecção por Leptospirose, e que essa resposta é dependente da espécie, bem como da virulência da bactéria.
Leptospirosis is a bacterial zoonosis of global importance, caused by Leptospira. The incidence of disease leading to one million severe cases and 60,000 deaths per year. Despite considerable advances in research, much is yet to be discovered about disease pathogenicity. The influence of epigenetic mechanisms, particularly RNA-mediated post-transcriptional regulation of host immune response has been proven vital following a variety of bacterial infections. The aim of this study was to identify and characterize, for the first time, the influence of miRNAs on the regulation of the immune response to Leptospira infection. We examined the microtranscriptome, trough microarray technique, of macrophages J774A.1 following an 8h infection with virulent, attenuated and saprophyte strains of Leptospira. Microarray analysis revealed that 29 miRNAs were de-regulated by the Leptospira strains compared to control with fold change ±1.5 and p-value <0.01. Enrichment analyses of the targets of these differentially expressed miRNAs suggest that several processes involved in immune response are directly regulated by miRNAs. We suggest that posttranscriptional regulation by miRNAs may play a role in host response to infection in leptospirosis, and that this response is dependent on species and bacterial virulence.
Leptospirosis is a bacterial zoonosis of global importance, caused by Leptospira. The incidence of disease leading to one million severe cases and 60,000 deaths per year. Despite considerable advances in research, much is yet to be discovered about disease pathogenicity. The influence of epigenetic mechanisms, particularly RNA-mediated post-transcriptional regulation of host immune response has been proven vital following a variety of bacterial infections. The aim of this study was to identify and characterize, for the first time, the influence of miRNAs on the regulation of the immune response to Leptospira infection. We examined the microtranscriptome, trough microarray technique, of macrophages J774A.1 following an 8h infection with virulent, attenuated and saprophyte strains of Leptospira. Microarray analysis revealed that 29 miRNAs were de-regulated by the Leptospira strains compared to control with fold change ±1.5 and p-value <0.01. Enrichment analyses of the targets of these differentially expressed miRNAs suggest that several processes involved in immune response are directly regulated by miRNAs. We suggest that posttranscriptional regulation by miRNAs may play a role in host response to infection in leptospirosis, and that this response is dependent on species and bacterial virulence.
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Palavras-chave
leptospirose, macrófagos, microRNA, leptospirosis, macrophage, miRNA