Role of Small RNAs in Trypanosomatid Infections

Abstract

Trypanosomatid parasites survive and replicate in the host by using mechanisms that aim to establish a successful infection and ensure parasite survival. Evidence points to microRNAs as new players in the host-parasite interplay. MicroRNAs are small non-coding RNAs that control proteins levels via post-transcriptional gene down-regulation, either within the cells where they were produced or in other cells via intercellular transfer. These microRNAs can be modulated in host cells during infection and are among the growing group of small regulatory RNAs, for which many classes have been described, including the transfer RNA-derived small RNAs. Parasites can either manipulate microRNAs to evade host-driven damage and/or transfer small RNAs to host cells. In this mini-review, we present evidence for the involvement of small RNAs, such as microRNAs, in trypanosomatid infections which lack RNA interference. We highlight both microRNA profile alterations in host cells during those infections and the horizontal transfer of small RNAs and proteins from parasites to the host by membrane-derived extracellular vesicles in a cell communication mechanism.

The enemy within: Targeting host–parasite interaction for antileishmanial drug discovery

“…Additionally, Leishmania interferes with the antigen-presentation capacity of their host cells through multiple mechanisms, implicating changes in abundance of costimulatory molecules or Major Histocompatibility Complex (MHC)-peptide complexes, destabilization of lipid rafts, or sequestration of Leishmania antigens [ 42 – 48 ]. Finally, Leishmania can interfere with the expression of microRNAs, which are considered as master regulators of the cellular transcriptome with important immunomodulatory functions (reviewed in [ 49 ]). In conclusion, a better understanding of how Leishmania interferes with macrophage immune functions may open important new venues to rescue the host cell’s immune potential by immunotherapy or immunochemotherapy, for example, using pro-inflammatory cytokines and chemokines alone or in combination with antileishmanial drugs (reviewed in [ 50 , 51 ]).…”

Modulation of miR-145-5p and miR-146b-5p levels is linked to reduced parasite load in H9C2 Trypanosoma cruzi infected cardiomyoblasts

“…MicroRNAs are noncoding single stranded RNA molecules of approximately 22 nucleotides, derived from hairpin structures and loaded into the argonaute protein of the silencing complex, forming imperfect base pairing with 3′-UTR of target sequences, thus repressing translation or promoting degradation of target mRNAs 20 , 21 . These RNA silencing molecules are usually involved in suppressing gene expression and have been found dysregulated in a variety of diseases, including a broad range of cardiac disorders 22 , 23 , bacterial 24 , viral 25 , 26 and parasite infections 27 – 30 . In CD, miRNA expression has been studied in heart tissue of transplanted CCC patients 31 , 32 , in a model of acute Chagas’ heart disease 33 , 34 and thymic epithelial cells from T. cruzi -infected mice 35 .…”

Invisible Designers: Brain Evolution Through the Lens of Parasite Manipulation

“…For example, viruses may induce the hosts to synthesize viral proteins by supplying strands of messenger RNA or directly insert copies of their genes into the host's DNA (retroviruses). Both protozoan and helminth parasites release vesicles containing small noncoding RNAs, which can regulate gene expression by host cells in myriad ways (e.g., Buck et al 2014;Cheeseman and Weitzman 2015;Linhares-Lacerda and Morrot 2016;Bayer-Santos et al 2017). All of these genomic/proteomic means of manipulation can be used to influence behavior.…”