Regulation of RNA-induced silencing complex by Leishmania: Targeting of host Argonaute-interactome

Author(s): Devki Nandan. Harsimran Kaur Brar, Atieh Moradimotlagh. Neil Reiner

Intracellular parasites of the genus Leishmania have coevolved to regulate host macrophage cell biology, enabling them to survive. It has become clear that small noncoding RNAs are involved in shaping innate and acquired immunity against pathogens. In most situations, small noncoding RNAs exert their functions via RNA interference (RNAi) pathway. It is known that proteins of the Argonaute (AGO) family play a critical role in RNAi as a part of the RNA-induced silencing complex. It is unsurprising that pathogens, including Leishmania regulate the RNAi pathway. Herein, we review evidence supporting the potential regulation of host macrophage RNAi machinery by Leishmania via targeting AGO proteins and associated proteins to create a pro-parasitic environment. A model is emerging that Leishmania performs de-facto cross-kingdom RNAi to regulate host gene expression and create a pro-parasitic climate leading to the development of chronic infection.