Extracellular Vesicles Derived From Entamoeba histolytica Have an Immunomodulatory Effect on THP-1 Macrophages

Recent studies have shown that extracellular vesicles (EVs) secreted by various parasites are capable of modulating the host's innate immune responses, such as by altering macrophage (M phi) phenotypes and functions. Studies have shown that M phi promote early host responses to amoebic infection by releasing proinflammatory cytokines that are crucial to combating amoebiasis. Here, we are reporting for the first time the effect of EVs released by Entamoeba histolytica (EhEVs) on human THP-1 differentiated M phi (THP-1 M phi). We show that the EhEVs are internalized by THP-1 M phi which leads to differential regulation of various cytokines associated with both M1 and M2 M phi. We also saw that EhEV treatment thwarted Type 2 immune-response-related transcriptome pSTAT6 in the THP-1 M phi. Furthermore, EhEVs stimulated M phi to reduce their energy demand by suppressing oxidative phosphorylation (OXPHOS) and adenosine triphosphate (ATP) production. Hence, the human parasite E. histolytica-derived EVs are capable of eliciting an immune response from M phi that may contribute to overall infection status.