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MicroRNAs e their mechanisms of gene regulation in symptomatic toxoplasmosis

Abstract

Recent studies have shown that microRNAs (miRNAs), which are small molecules, play an important role in regulation of gene expression in eukaryotic cells are able of negatively regulating the processing, stability and translation of several target messenger RNAs for cytokine production. However, the regulatory mechanisms involved during infection by Toxoplasma gondii are still unknown. Our findings on characterization of immune response of patients with symptomatic toxoplasmosis (ocular and cerebral) identified potential miRNAs that could be involved in regulating the production of important cytokines for infection control. These data led us to investigate the characterization of immune response of one of the most important clinical forms of toxoplasmosis, the congenital form. Thus, the objective of this project is to assess the levels of miRNAs and cytokines in paired samples from mother (serum / plasma of pregnant women with acute toxoplasmosis) and fetus (amniotic fluid) in order to identify potential miRNAs that are markers of congenital infection. Next, the differentially expressed miRNAs will be subjected to in silico analysis and their predicted targets will be determined. Finally, even with the impossibility of isolating the parasite strain present in clinical samples, we intend to establish an in vitro model of cell culture infected with RH strain of T. gondii to continue the study in order to validate the results of the bioinformatics analysis and confirm the potential effects of miRNAs on their targets through the in vitro functional characterization of selected miRNAs. Furthermore, we intend to measure its effects on cellular processes and its impact on the production of cytokines that are important for infection control. We believe that investigation of mRNA role in playing in regulation of immune system is timely and relevant. Since recent studies are looking for miRNAs that could be biomarkers of complications associated with pregnancy, little is known in the context of infectious and parasitic diseases, such as congenital toxoplasmosis. Thus, the study of new markers of congenital infection could assist in the development of new diagnostic tools, implying a more aggressive therapy, in the prognosis of infection, in the study of new therapeutic targets and provide a greater understanding of the poorly studied mother-fetus binomial. (AU)

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