Lecture by Dr. Devki Nandan from the University of British Columbia

We invite you to an open lecture titled “Leishmania targets host RNA interference machinery to promote its survival.” The lecture will take place on Thursday, June 27, 2024, from 3:00 PM to 4:30 PM at the Faculty of Biology, University of Warsaw, Ilji Miecznikowa Street 1, room 103/B. The lecture will be delivered in English.

Dr. Devki Nandan is an assistant professor in the Division of Infectious Diseases at the University of British Columbia. He specializes in studying host-pathogen interactions, particularly focusing on Leishmania donovani, a pathogen causing visceral leishmaniasis. His research investigates how Leishmania manipulates host macrophages to survive and replicate. Dr. Nandan holds a Ph.D. in Biochemistry from the University of Western Ontario.

Abstract:
Leishmaniasis is a spectrum of diseases caused by protozoan parasites of the genus Leishmania. The most severe form of disease is visceral leishmaniasis caused by Leishmania donovani. In humans, Leishmania primarily resides in macrophages, cells that eliminate intracellular pathogens. Over the years, it has become clear that Leishmania has evolved to develop strategies to survive in the hostile environment of macrophages. Non-coding RNAs (ncRNAs) play essential roles in many biological processes and diseases. Complexes of Argonaute (Ago) proteins with small ncRNAs are central to RNA interference, also known as RNA-induced silencing complexes (RISCs). Evidence has accumulated that several intracellular pathogens target host cell RNAi to promote survival.

Recently, we investigated the possibility that Leishmania targets host macrophage Ago(s) to facilitate its survival. We found that Leishmania infection selectively upregulated the abundance of macrophage Ago1, resulting in higher levels of Ago1 in active Ago complexes, suggesting the preferred use of Ago1 in RNAi in Leishmania-infected cells. Deliberate Ago1 silencing attenuated intracellular survival of Leishmania, demonstrating that Ago1 is essential for Leishmania pathogenesis. To further investigate the role of macrophage Ago1 in Leishmania pathogenesis, a quantitative proteomic was employed, which showed that the expression of several previously reported Leishmania pathogenesis-related proteins was dependent on the level of macrophage Ago1. Biochemical characterization of the proteome of macrophage Agos interactome isolated from infected cells revealed Leishmania modulated macrophage RISCs composition during infection. Strikingly, Leishmania proteins were detected as part of host Ago-containing complexes in infected cells. These results suggest targeting the core component of host RNAi machinery. Together, these findings identified Ago1 as the preferred Argonaute of RNAi machinery in infected cells and a novel and essential virulence factor by proxy that promotes Leishmania survival. Additionally, these results expand knowledge of RISC in the context of host-pathogen interactions in parasitology in general.