miRNome Expression Analysis Reveals New Players on Leprosy Immune Physiopathology

Mycobacterium leprae is an uncultivatable obligate intracellular human pathogen that causes leprosy that mainly causes damage to skin and peripheral nerves, resulting in a range of skin lesions, peripheral neuropathy, anesthesia and bone resorption with related disfigurement, deformity and disability along with the social stigma intimately associated with this ancient disease. Despite the use of multidrug therapy since the 80´s, over 200,000 new cases are still reported yearly, indicating active transmission, like in Brazil. In light of recent studies regarding host-pathogen miRNA changes, we investigated the first miRNome expression profile of leprosy patients at the two polar ends of the clinical spectrum (tuberculoid and lepromatous) compared to healthy control individuals. Biopsies from skin lesions (6 LL-pole and 5 TT-pole) and 11 samples (5 LL-pole and 4 TT-pole) of peripheral blood of leprosy patients were collected. After extraction, RNA was submitted to next generation sequencing on an Illumina platform. The results obtained were normalized and analyzed using the package Bioconductor-DESeq2 with statistic software R. The differential expression profile from tissue samples revealed 67 discrete miRNAs, 43 that were downregulated and 24 that were upregulated, while in blood samples, only 10 discrete miRNAs were revealed, with 9 downregulated and one upregulated. Additionally, an in silico target analysis for detected genes involved in the pathology of leprosy was performed. Among these miRNAs, hsa-miR-1291, which regulates the aquaporin-1 (AQP1) gene, was found to be differentially expressed in both blood and tissue samples from leprosy patients. This gene is related to skin permeability and could help explain some the known clinical issues of leprosy involving the skin. Furthermore, four miRNAs were found to be differentially expressed between the two main forms of leprosy and could be used to improve diagnosis and treatment.