MicroRNAs controlam a infecção por Toxoplasma gondii e Neospora caninum in vitro

Abstract

MicroRNAs (miRNAs) are small endogenous non-coding RNAs that regulate post-transcriptional gene expression and are found in all conserved eukaryotic cells across species. In recent years, the regulation of miRNAs has been thoroughly studied due to the key role these small RNAs play in biological processes. They have a crucial role in regulation, influencing various biological processes, and are promising as disease biomarkers, with effective profiles for several other therapeutic applications, including potential treatments for diseases that still pose risks to society. This work focuses on evaluating the role of miRNAs in infections caused by the intracellular parasites Toxoplasma gondii and Neospora caninum, which raise concerns in public health and the livestock industry, respectively. Through bioinformatics analyses, differential miRNA expression was identified during parasitic infection, highlighting miR-6236, which showed significant regulation in N. caninum infections. The analysis also included miR-155, a widely studied miRNA for its role in immunity, as a comparative target to validate the findings. Genetic editing of L929 fibroblasts using the CRISPR/Cas9 system was performed to deplete the selected miRNAs, allowing the investigation of the impact of these molecules on infection susceptibility. The results showed that knockout cells for miR-6236 and miR-155 displayed increased susceptibility to infection, suggesting that these miRNAs play a protective role in modulating the immune response against these parasites. Additionally, miR-6236 was associated with the regulation of genes important for controlling inflammatory responses and defense processes. Based on these findings, it is concluded that the study of specific miRNAs during infections by T. gondii and N. caninum may provide new insights into parasite-host interactions and identify potential therapeutic targets for controlling these infections, particularly regarding the modulation of innate and adaptive immunity.