Hijacking Host Communication: The Central Role of Extracellular Vesicles in Infectious Disease Pathogenesis

Extracellular vesicles (EVs) have emerged as fundamental mediators of intercellular communication during infectious diseases, acting as vehicles for proteins, lipids, and nucleic acids that profoundly influence host-pathogen interactions. In recent years, accumulating evidence has revealed that pathogens from distinct biological kingdoms, including protozoan parasites, viruses, and bacteria, either release their own EVs or exploit host-derived EVs to manipulate immune responses, promote infection, and sustain chronic disease. This review provides a comprehensive and integrative overview of the roles of EVs in infectious diseases, with particular emphasis on immune modulation, immune evasion, pathogenesis, and translational applications. We summarize current knowledge on EV-mediated communication in infections caused by major protozoan parasites (Trypanosoma cruzi, Plasmodium spp., Toxoplasma gondii, and Leishmania spp.), highlighting how parasite- and host-derived EVs regulate inflammatory responses, facilitate intracellular survival, and shape disease outcomes. We further examine viral infections, including HIV, HPV, HCV, and airborne respiratory viruses such as SARS-CoV-2, where EVs contribute to viral persistence, immune dysfunction, oncogenesis, and long-term sequelae. In addition, we discuss bacterial infections, focusing on Mycobacterium tuberculosis, Streptococcus pneumoniae, and Helicobacter pylori, illustrating how EVs can function both as vectors of virulence factors and as components of host defense mechanisms. Finally, we explore the emerging translational potential of EVs as non-invasive biomarkers for disease diagnosis and prognosis, as well as their application as therapeutic and vaccine platforms. By integrating findings across diverse pathogens, this review highlights extracellular vesicles as widely implicated and dynamic contributors of infectious disease biology and underscores their relevance as targets and tools for next-generation diagnostic and therapeutic strategies.