Leishmania Exosomal tRNA-Derived Small Non-Coding RNA Fragments Modulate Host THP-1 Derived Macrophage Proteins: A Quantitative Proteomic An
Researchers investigated how Leishmania exosomal Ld-tRFs influence host cell function. Synthetic fragments were used to analyze effects on the macrophage proteome.
Protozoan parasites of the genus Leishmania are responsible for human leishmaniasis and have evolved sophisticated mechanisms to manipulate host cell functions. Recent studies have identified small non-coding RNAs as contributors to pathogenesis, with specific tRNA-derived fragments (tRFs) being delivered via exosomes to influence host responses.
This study employed SILAC-based quantitative proteomics to investigate the effects of synthetic Leishmania tRNA-derived fragments on THP-1-derived macrophages. Researchers analyzed how Ld-tRF-Asp and Ld-tRF-Leu affect the macrophage proteome, providing a systematic approach to understanding these molecular interactions.
The findings revealed that Ld-tRF-Asp modulated 20 proteins while Ld-tRF-Leu affected 18 proteins in macrophages. Notably, seven of each protein set showed potential pro-Leishmania effects, suggesting these fragments may facilitate parasite survival within the host environment.
Biochemical isolation of Argonaute (Ago) protein complexes followed by identification of interacting small non-coding RNAs demonstrated selective presence of both tRFs in Leishmania-infected macrophages. This suggests Ld-tRFs engage macrophage Ago proteins for their effects, with an in vivo biotin-RNA pull-down assay indicating Ago 1 is the preferred guide.
Taken together, this study shows that Leishmania exosomal tRFs significantly alter the host macrophage proteome in favor of Leishmania survival. These findings offer new insights into leishmaniasis mechanisms and may provide future therapeutic interventions targeting these regulatory molecules.