Extracellular vesicles derived from Plasmodium falciparum-infected red blood cells transfer miR451a, disrupting neutrophil function and contributing to immune dysregulation

Here, we demonstrate that the malaria parasite utilizes extracellular vesicles (EVs) derived from infected red blood cells (iRBC-EVs) as a mechanism to transfer the host microRNA miR451a to primary human neutrophils, effectively suppressing their immune functions. Using primary human neutrophils and transduced Human leukemia cell (HL-60 cells) with a lentiviral expression vector containing miR451a (HL-60miR451a), we evaluated the effect of miR451a in neutrophil transcription and effector functions (ROS production, swarming and antimicrobial activity).

The microfluidic assay shows that the transferred miR451a significantly reduces chemotaxis and swarming ability of both primary human neutrophils and HL-60miR451a when subsequently challenge with Candida albicans. Bulk and single cell transcriptomic analysis reveals that miR451a alters transcriptional regulation in primary both neutrophils and HL-60miR451a, further impairing their immune responses . Additionally, we demonstrate that phagocytosed iRBC-EVs blunt the production of reactive oxygen species (ROS) and reduce the anti-microbicidal activity of neutrophils upon Salmonella typhimurium challenge.