Abstract
BackgroundChagas disease is considered important and presents intense inflammatory and fibrotic processes induced by the perpetuation of the parasite in the affected tissues and organs. Therefore, it is necessary to inquire about the host defense and attack mechanisms to have a more detailed knowledge about Chagas disease. MicroRNAs are found in blood, tissues and extracellular vesicles. These small regulators of gene expression are involved in physiological and pathological processes in both mammals and parasites. Several microRNAs have deregulated expression in chagasic heart disease, although little is known about their extracellular expression. Our main objective was to evaluate the involvement of miR-21, miR-146a and miR-155 in several samples from mice infected with the TcI Ninoa strain from the acute and indeterminate phases. We also explored a potential functional association of the selected microRNAs using STRING software. This software identified 23 pathways associated with Trypanosoma cruzi infection. In addition, eleven genes were identified through bioinformatics analysis, and we found that SMAD family member 5 was downregulated in both phases. This gene serves as a mediator in the TGF-β signaling pathway. Thus, forty female mice of the CD1 strain were distributed into 4 groups and the expression levels of miR-21, miR-146a and miR-155 were measured in samples of heart tissue, total plasma and plasma extracellular vesicles by quantitative real-time polymerase chain reaction.ResultsOverexpression of miR-21, miR-146a and miR-155 was observed in heart and plasma in both phases. Moreover, in extracellular vesicles miR-21 and miR-146a were also overexpressed in the acute phase, whereas in the indeterminate chronic phase we found only miR-146a up-regulated.ConclusionsThe expression of inflammatory microRNAs miR-21, miR-146a and miR-155 were up-regulated in each of the samples from acutely and chronically infected mice. The relevant finding was that miR-146a was up-regulated in each sample in both phases; therefore, this miRNA could be a possible candidate biomarker in Chagas disease.
Highlights
Chagas disease is considered important and presents intense inflammatory and fibrotic processes induced by the perpetuation of the parasite in the affected tissues and organs
The analysis revealed 23 STRING-Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in Mus musculus that were associated with T. cruzi infection and Chagas disease according to an extensive literature review; the pathways predicted as the most markedly enriched by the three miRNAs mentioned above were PI3K-Akt, Chemokines, Fig. 3 A Particles distribution, B particles counting and C miRNAs expression of Extracellular vesicles (EVs) in the acute phase
Studies in humans and mice have shown that the inflammatory reaction observed in chagasic cardiomyopathy (CCC) is similar to delayed-type hypersensitivity (DTH) composed of mononuclear cells, mainly CD4+ Th1 cells
Summary
Chagas disease is considered important and presents intense inflammatory and fibrotic processes induced by the perpetuation of the parasite in the affected tissues and organs. Micro‐ RNAs are found in blood, tissues and extracellular vesicles These small regulators of gene expression are involved in physiological and pathological processes in both mammals and parasites. Chagas disease is due to intense inflammatory injury and induced fibrosis in tissues and organs involved in the infectious cycle of the parasite. If this disease is not treated in time, it can damage the heart muscle tissue, leading to chronic chagasic cardiomyopathy (CCC). One of mechanisms of Chagas pathogenesis is to lead toward parasite products, cellular invasion and intracellular replication Another is by the implication of the cellmediated immunity, such as T cells with Th1 and Th17 response and the humoral immunity that is characterized by polyclonal activation of B cells. These mechanisms explain the host response to T. cruzi infection and the adaptative immunity to T. cruzi infection [2]
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