Study of differential expression of miRNAs in lung tissue of mice submitted to experimental infection by Paracoccidioides brasiliensis.

Abstract

MicroRNAs (miRNAs) are small single stranded RNA sequences involved in post-transcriptional regulation of different biological and physiological processes. Paracoccidioidomycosis (PCM) is an infection caused by Paracoccidioides brasiliensis, and it is a major cause of mortality due to systemic mycoses in Brazil. To date, there have been few reports on the role of miRNAs in the immune response against fungi, especially PCM. The objective of this study was to evaluate the differential expression of miRNAs related to the inflammatory response associated with pulmonary infection by P. brasiliensis. For this purpose, lungs from BALB/c mice, intravenously infected with P. brasiliensis (2.7×107 yeast cells/ml, n = 12) and noninfected BALB/c mice (n = 8), were collected at the 28 and 56 day after infection. The lung parenchyma presented a great number of yeast cells, granulomas, and edema at 28 days and a framework of resolution of the inflammatory process after 56 days. The mRNAs gata-3, ror-γt, foxp3, and IL-6 were positively regulated at the moment at the 56 day, while the TGF-β1 mRNA was positively regulated at both moments. The miRNAs 126a-5p, 340-5p, 30b-5p, 19b-3p, 221-3p, 20a-5p, 130a-3p, and 301a-3p, 466k presented the greatest increase in expression levels 28 days after infection, and the miRNAs let-7f-5p, let-7a-5p, 5p-26b, let-7e-5p and 369-3p, 466k presented a greater increase in levels of expression 56 days after infection. This study shows a set of differentially expressed miRNAs possibly involved in the immune response in mice during pulmonary infection by P. brasiliensis.