Extracellular vesicles in intestinal protozoa: hidden mediators of host-parasite communication

Intestinal protozoan parasites, including, Cryptosporidium spp., Giardia duodenalis, Entamoeba histolytica, and Blastocystis sp. pose significant global health challenges, particularly in developing regions with limited access to sanitation and healthcare resources. Extracellular vesicles (EVs) have emerged as critical factors for communication in the complex interplay between intestinal protozoan parasites and their hosts. This review explores the diverse roles of parasite-derived EVs, with a focus on their biogenesis, molecular cargo, and host interactions. Studies show that G. duodenalis EVs disrupt tight junctions in intestinal epithelia and promote Th1 immune responses. Blastocystis sp. EVs modulate cytokine production, increasing IL-6 and TNF-α while reducing IL-10 and IL-4. E. histolytica EVs inhibit immune cell recruitment by downregulating STAT6 signaling and suppressing IL-4 and IL-13. Additionally, Cryptosporidium-infected epithelial cells release EVs enriched in GP60 and CpRom1 proteins that stimulate host immune responses via the TLR4/IKK pathway. Beyond pathogenesis, the specific and stable cargo of parasitic EVs supports their utility as biomarkers and therapeutic agents. Ongoing research into their roles in microbiome modulation and immune regulation may inform future diagnostics and treatments for parasitic infections.