MiR-4792 regulates inflammatory responses in Cryptococcus neoformans infected microglia

Abstract

Background: Investigating the factors that influence inflammatory response of microglial cells is important to understand the pathogenesis of cryptococcal meningitis (CM). MicroRNA (miRNA) have been shown to play an important role in inducing host defenses and activating immune response in the process of microbial infection; however, the regulatory mechanisms of miRNAs in cryptococcal meningitis are poorly defined. In our previous analysis, we assessed the miRNA profiles of BV2 cells following Cryptococcus neoformans (C. neoformans) infection. In this study, we characterized the expression of miR-4792 in CM patients to further our understanding of the host response to pathogen infections.Results: miR-4792 was downregulated in BV2 cells infected with C. neoformans while its target gene EGFR was upregulated. Infected cells with up-regulated miR-4792 exhibited decreased EGFR expression, reduced MAPK signaling and a decreased secretion of inflammatory cytokines. Following antifungal treatment in cryptococcal meningitis patients, the levels of miR-4792 in the CSF significantly increased, while the expression of EGFR significantly decreased.Conclusion: This study identified that miR-4792 and its target EGFR regulate the secretion of inflammatory cytokines in C. neoformans infected BV2 cells. This furthers our knowledge of the host immune responses to fungal infections in the CNS.