Extracellular Vesicles in Malaria: Shedding Light on Pathogenic Depths

Abstract

Malaria, a life-threatening infectious disease caused by Plasmodium falciparum, remains a significant global health challenge, particularly in tropical and subtropical regions. The epidemiological data for 2021 revealed a staggering toll, with 247 million reported cases and 619,000 fatalities attributed to the disease. This formidable global health challenge continues to perplex researchers seeking a comprehensive understanding of its pathogenesis. Recent investigations have unveiled the pivotal role of extracellular vesicles (EVs) in this intricate landscape. These tiny, membrane-bound vesicles, secreted by diverse cells, emerge as pivotal communicators in malaria's pathogenic orchestra. This Review delves into the multifaceted roles of EVs in malaria pathogenesis, elucidating their impact on disease progression and immune modulation. Insights into EV involvement offer potential therapeutic and diagnostic strategies. Integrating this information identifies targets to mitigate malaria's global impact. Moreover, this Review explores the potential of EVs as diagnostic biomarkers and therapeutic targets in malaria. By deciphering the intricate dialogue facilitated by these vesicles, new avenues for intervention and novel strategies for disease management may emerge.

Cerebral Malaria: Clinicians, Extracellular Vesicles, and Therapeutically-Rational Exchange (T-REX)

“…PfEMP1 proteins incorporated into ECs and immune cells can promote inflammation [6,105] TIM-1 and TIM-4 (on immune cells and possibly on brain microglia) Immune-cell activation [6,7,95] BAI-1 (on neurons and cerebral ECs) [6] Relevant to the confusion surrounding the role of the CD36 cell receptor in CM, our review identified studies (and expert reviews) indicating that although cerebral ECs may express little CD36, iRBC-platelet-EC "bridge binding" within cerebral microvessels means the CD36 expressed by platelets can cause CD36-dependent microvascular obstruction in CM [9]. A study of children with malaria showed all Pf-parasite isolates but 1 (70 of 71) bound to CD36 [51].…”

“…MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions, or products referred to in the content. 2 phosphatidylserine (PS) which is a key ligand in Pf infection [7]. Adhesive PfEMP1-expressing iRBCs can cause mechanical microvessel obstruction that can substantially reduce blood flow, damage tissues (like vascular endothelium), and trigger inflammation.…”