Abstract

Introduction The airway epithelium plays a crucial role in the entry of Mycobacterium tuberculosis (Mtb) to the respiratory tract. MiRNAs are involved in regulating the immune response against infections. Better tools are urgently required to diagnose early tuberculosis infection. In this study, we analyzed miRNA expression of nasopharyngeal mucosa in subjects with recent exposure to Mtb in order to gain a better understanding of tuberculosis pathogenesis and to determine the role of miRNA in TB acquisition risk. Methods Thirty-one uninfected and thirteen asymptomatic household contacts with newly acquired latent tuberculosis (LTBI) were recruited. LTBI status was defined by serial interferon-gamma release assay testing at baseline and follow-up. Nasopharyngeal swabs were sampled and stored at -80ºC until RNA extraction. Extracted RNA samples were sequenced and miRNA differential expression was analyzed with DESeq2 package in R (p<0.05 was considered as statistically significant and log fold change >1.5). Results Thirty-six miRNAs showed significantly and differential expression, with 28 miRNAs exhibiting higher expression in the newly acquired LTBI group compared to uninfected individuals. Hierarchical clustering revealed two major miRNA clusters differentiating subjects with newly acquired LTBI from those uninfected. Moreover, individuals with newly acquired LTBI were divided in two separate clusters with distinct expression pattern. Conclusions A miRNA expression pattern significantly discriminated between uninfected household contacts from those with newly acquired LTBI infection, who additionally were separated into 2 clusters. Validation of these miRNAs with RT-qPCR is required, as well as additional larger studies to corroborate these results. FONDECYT Regular 1171570 and 1191874.