Abstract

BACKGROUND Paracoccidioides spp. causes paracoccidioidomycosis (PCM), an important and frequent systemic mycosis that occurs in Latin America. The infectious process begins with contact between the fungus and lung cells, and the molecular pattern of this interaction is currently poorly understood. MicroRNAs (miRNAs) are small non-coding RNAs that regulate the gene expression in many biological processes, including in the infections.OBJECTIVE This study aimed to analyse the expression of miRNAs in lung cells as response to infection by Paracoccidioides spp.METHODS A quantitative real-time polymerase chain reaction (RT-qPCR) based screening was employed to verify differentially expressed miRNAs in human lung cells infected with three different species; Paracoccidioides lutzii, Paracoccidioides americana, and Paracoccidioides brasiliensis. Furthermore, the in silico predictions of target genes and pathways for miRNAs were obtained.FINDINGS The results showed that miRNAs identified in the lung cells were different according to the species studied. However, based on the predicted targets, the potential signaling pathways regulated by miRNAs are common and related to adhesion, actin cytoskeleton rearrangement, apoptosis, and immune response mediated by T cells and TGF-β.MAIN CONCLUSIONS In summary, this study showed the miRNAs pattern of epithelial cells in response to infection by Paracoccidioides species and the potential role of these molecules in the regulation of key pathogenesis mechanisms of PCM.

Highlights

  • Paracoccidioides spp. causes paracoccidioidomycosis (PCM), an important and frequent systemic mycosis that occurs in Latin America

  • Paracoccidioidomycosis (PCM) is a systemic mycosis, endemic in Latin America. This mycosis is acquired after inhalation of conidia of dimorphic fungus Paracoccidioides spp. and the infectious process begins in the lungs of patients, but the fungus can spread to other organs.[1]. The Paracoccidioides genus is composed of a clade with five phylogenetic species: Paracoccidioides brasiliensis (S1a, S1b, PS2, PS3, and PS4) and a Paracoccidioides lutzii clade.[2,3] Recently, a new taxonomic description was suggested, wherein phylogenetic species PS2, PS3, and PS4 were reclassified as species Paracoccidioides americana, Paracoccidioides restrepiensis and Paracoccidioides venezuelensis, respectively.[4]. In this context, the correct molecular taxonomy of these fungi has opened new possibilities for studying and understanding their relationships with their hosts.[5]

  • In the cells infected with P. brasiliensis 18 (Pb18), eight miRNAs were upregulated and 10 miRNAs down-regulated compared to the control (Table III)

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Summary

BACKGROUND

Paracoccidioides spp. causes paracoccidioidomycosis (PCM), an important and frequent systemic mycosis that occurs in Latin America. MicroRNAs (miRNAs) are small non-coding RNAs that regulate the gene expression in many biological processes, including in the infections

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