Abstract
Pathogens have evolved mechanisms to modulate host cell functions and avoid recognition and destruction by the host damage response. For many years, researchers have focused on proteins as the main effectors used by pathogens to hijack host cell pathways, but only recently with the development of deep RNA sequencing these molecules were brought to light as key players in infectious diseases. Protozoan parasites such as those from the genera Plasmodium, Toxoplasma, Leishmania, and Trypanosoma cause life-threatening diseases and are responsible for 1000s of deaths worldwide every year. Some of these parasites replicate intracellularly when infecting mammalian hosts, whereas others can survive and replicate extracellularly in the bloodstream. Each of these parasites uses specific evasion mechanisms to avoid being killed by the host defense system. An increasing number of studies have shown that these pathogens can transfer non-coding RNA molecules to the host cells to modulate their functions. This transference usually happens via extracellular vesicles, which are small membrane vesicles secreted by the microorganism. In this mini-review we will combine published work regarding several protozoan parasites that were shown to use non-coding RNAs in inter-kingdom communication and briefly discuss future perspectives in the field.
Highlights
Protozoan parasites comprise an exceptionally diverse group of unicellular eukaryotic organisms
The main RNA-induced silencing complex (RISC) components (Argonaute, Piwi, Dicer, RNAse III) and miRNAs have been identified in Trypanosoma brucei, Trypanosoma congolense, Leishmania (V.) braziliensis, T. gondii, Neospora caninum, G. lamblia, Trichomonas vaginalis and E. histolytica, suggesting that these organisms have a classical RNA interference (RNAi) pathway (Militello et al, 2008; Atayde et al, 2011, 2013; Hakimi and Cannella, 2011; Kolev et al, 2011; Zheng et al, 2013)
Protozoan parasites may modulate the expression of host miRNAs associated with different biological processes in order to survive in the intracellular environment
Summary
Protozoan parasites comprise an exceptionally diverse group of unicellular eukaryotic organisms. Protozoan parasite-host cell interplay can occur directly by physical cell-cell contact or indirectly via secreted/excreted molecules, which can be released into the extracellular medium or packed into extracellular vesicles (EVs) (reviewed in Torrecilhas et al, 2012; Barteneva et al, 2013; Deolindo et al, 2013; Mantel and Marti, 2014; Marcilla et al, 2014; Judice et al, 2016; Marti and Johnson, 2016; Roditi, 2016; Szempruch et al, 2016a; Watanabe Costa et al, 2016). The packaging of proteins and nucleic acids, such as small non-coding RNAs (sncRNAs), in EVs protects them from extracellular degradation until they reach the target recipient cell. Transference of proteins and RNAs within EVs seems to be a safe mechanism for local and systemic intercellular interactions between parasites and host cells, and between parasites themselves. We present the current understanding of sncRNAs in protozoan parasites and provide examples of their role during infections
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