Extracellular vesicles in malaria pathogenesis and Therapy: Emerging insights and future perspectives

Malaria remains a major global health challenge, responsible for millions of cases and substantial mortality each year. The emergence of drug-resistant strains and the lack of an effective vaccine underscore the urgent need for novel therapeutic strategies. Recent research has highlighted the pivotal role of extracellular vesicles (EVs), particularly small EVs derived via the endosomal pathway—commonly known as exosomes—in the progression of malaria and modulation of immune responses. These exosomes carry bioactive molecules that influence both innate and adaptive immunity. The biogenesis of exosomes is regulated by various cellular factors, and their involvement in host-pathogen interactions has revealed complex molecular mechanisms underlying parasitic diseases. This review provides an overview of exosome biogenesis, their molecular cargo, and their functional roles in malaria pathogenesis. Within this context, the growing interest in exosomes as therapeutic targets is discussed, given their immunomodulatory potential and utility as biomarkers for disease diagnosis and prognosis. Furthermore, we explore the significance of three-dimensional (3D) cell culture systems and in vivo models in elucidating exosome-mediated host-parasite interactions, emphasizing their contribution to advancing malaria research. Finally, we address current developments and future perspectives in the field, advocating for exosome-based interventions as a promising new paradigm in malaria therapy. This review aims to offer a comprehensive overview of the interplay between malaria and exosomes, opening avenues for innovative diagnostic and therapeutic approaches.