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MicroRNAs (miRNAs) are a group of small non-coding RNAs present in a wide diversity of organisms. MiRNAs regulate gene expression at a post-transcriptional level through their interaction with the 3′ untranslated regions of target mRNAs, inducing translational inhibition or mRNA destabilization and degradation. Thus, miRNAs regulate key biological processes, such as cell death, signal transduction, development, cellular proliferation and differentiation. The dysregulation of miRNAs biogenesis and function is related to the pathogenesis of diseases, including parasite infection. Moreover, during host–parasite interactions, parasites and host miRNAs determine the probability of infection and progression of the disease. The present review is focused on the possible role of miRNAs in the pathogenesis of diseases of clinical interest caused by parasitic protists. In addition, the potential role of miRNAs as targets for the design of drugs and diagnostic and prognostic markers of parasitic diseases is also discussed.

microRNAs (miRNAs) are a group of small non-coding RNAs that regulate gene expression post-transcriptionally through their interaction with the 3′ untranslated regions (3′ UTR) of target mRNAs, affecting their stability and/or translation. Therefore, miRNAs regulate biological processes such as signal transduction, cell death, autophagy, metabolism, development, cellular proliferation, and differentiation. Dysregulated expression of microRNAs is associated with infectious diseases, where miRNAs modulate important aspects of the parasite–host interaction. Helminths are parasitic worms that cause various neglected tropical diseases affecting millions worldwide. These parasites have sophisticated mechanisms that give them a surprising immunomodulatory capacity favoring parasite persistence and establishment of infection. In this review, we analyze miRNAs in infections caused by helminths, emphasizing their role in immune regulation and its implication in diagnosis, prognosis, and the development of therapeutic strategies.

Apicomplexans are a group of pathogenic protists that cause various diseases in humans and animals that cause economic losses worldwide. These unicellular eukaryotes are characterized by having a complex life cycle and the ability to evade the immune system of their host organism. Infections caused by some of these parasites affect millions of pregnant women worldwide, leading to various adverse maternal and fetal/placental effects. Unfortunately, the exact pathogenesis of congenital apicomplexan diseases is far from being understood, including the mechanisms of how they cross the placental barrier. In this review, we highlight important aspects of the diseases caused by species of Plasmodium, Babesia, Toxoplasma, and Neospora, their infection during pregnancy, emphasizing the possible role played by the placenta in the host-pathogen interaction.

Congenital Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is responsible for 22.5% of new cases each year. However, placental transmission occurs in only 5% of infected mothers and it has been proposed that the epithelial turnover of the trophoblast can be considered a local placental defense against the parasite. Thus, Trypanosoma cruzi induces cellular proliferation, differentiation, and apoptotic cell death in the trophoblast, which are regulated, among other mechanisms, by small non-coding RNAs such as microRNAs. On the other hand, ex vivo infection of human placental explants induces a specific microRNA profile that includes microRNAs related to trophoblast differentiation such as miR-512-3p miR-515-5p, codified at the chromosome 19 microRNA cluster. Here we determined the expression validated target genes of miR-512-3p and miR-515-5p, specifically human glial cells missing 1 transcription factor and cellular FLICE-like inhibitory protein, as well as the expression of the main trophoblast differentiation marker human chorionic gonadotrophin during ex vivo infection of human placental explants, and examined how the inhibition or overexpression of both microRNAs affects parasite infection. We conclude that Trypanosoma cruzi-induced trophoblast epithelial turnover, particularly trophoblast differentiation, is at least partially mediated by placenta-specific miR-512-3p and miR-515-5p and that both miRNAs mediate placental susceptibility to ex vivo infection of human placental explants. Knowledge about the role of parasite-modulated microRNAs in the placenta might enable their use as biomarkers, as prognostic and therapeutic tools for congenital Chagas disease in the future.

Trypanosoma cruzi and Toxoplasma gondii are two parasites than can be transmitted from mother to child through the placenta. However, congenital transmission rates are low for T. cruzi and high for T. gondii. Infection success or failure depends on complex parasite-host interactions in which parasites can alter host gene expression by modulating non-coding RNAs such as miRNAs. As of yet, there are no reports on altered miRNA expression in placental tissue in response to either parasite. Therefore, we infected human placental explants ex vivo by cultivation with either T. cruzi or T. gondii for 2 h. We then analyzed the miRNA expression profiles of both types of infected tissue by miRNA sequencing and quantitative PCR, sequence-based miRNA target prediction, pathway functional enrichment, and upstream regulator analysis of differentially expressed genes targeted by differentially expressed miRNAs. Both parasites induced specific miRNA profiles. GO analysis revealed that the in silico predicted targets of the differentially expressed miRNAs regulated different cellular processes involved in development and immunity, and most of the identified KEGG pathways were related to chronic diseases and infection. Considering that the differentially expressed miRNAs identified here modulated crucial host cellular targets that participate in determining the success of infection, these miRNAs might explain the differing congenital transmission rates between the two parasites. Molecules of the different pathways that are regulated by miRNAs and modulated during infection, as well as the miRNAs themselves, may be potential targets for the therapeutic control of either congenital Chagas disease or toxoplasmosis.