Abstract
Abstract Regulation of microRNAs has been shown to be critical in immune cell development as well as the progression of certain cancers. However, their role in immune response to microbial infection has remained elusive. We chose to use Mycobacterium leprae, the causative agent of leprosy, as a model to determine the potential roles of microRNA in pathogenesis. The immune response to M. leprae has been well-characterized as presenting as a spectrum, ranging from a more contained Th1 response in tuberculoid patients to a more disseminated Th2 response in lepromatous patients, providing a good system for examining the correlation of microRNAs and type of immune response. We performed mRNA and microRNA microarray analysis on 6 T-lep and 6 L-lep lesions to determine whether microRNA disregulation and subsequent downregulation of key immune genes contributes to the outcome and morbidity of infection. We discovered 7 microRNAs in T-lep and 28 microRNAs in L-lep lesions and cross-referenced them in MiRNA and Genes Integrated Analysis (MAGIA) web tool with mRNA gene transcripts that were significantly downregulated in the same lesions. Preliminary analysis of Th1 and Th2 gene targeting shows microRNAs more highly expressed in L-lep lesions may preferentially target proinflammatory genes, which could explain the bias in immune response to infection.
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