Extracellular vesicles and mononuclear phagocyte axis: Interactions shaping immune responses

Extracellular vesicles (EVs), nano-sized particles enclosed by a lipid membrane, play a pivotal role in cell-to-cell communication as essential mediators in various biological processes and diseases. Despite their ability to interact with multiple targets, EVs notably demonstrate a high affinity for specialized cells within the extracellular environment, particularly mononuclear phagocytes. The interaction between EVs and mononuclear phagocytes significantly affects the profile of these cells. Several factors, including vesicle cargo, size, parental cell origin, involved receptors, and the specific endocytic pathway, influence EVs' consequences and subsequent responses. Key components of mononuclear phagocytes, monocytes and macrophages, play a crucial role in the innate immune system, contributing to tissue damage, repair, remodeling, inflammation, homeostasis maintenance, and disease progression. Despite extensive research on EVs in various health and disease contexts, their precise impact on mononuclear phagocytes remains incompletely understood. Therefore, this review explores EVs' role in modulating monocyte and macrophage profiles and functions across different scenarios. It emphasizes that EVs actively shape the phenotype of these mononuclear phagocytes to maintain homeostasis and regulatory functions, but also induce pro-inflammatory polarization in infectious diseases, systemic inflammation, and autoimmunity. Simultaneously, during neoplastic or tumor development, the EV-mononuclear phagocyte axis prompts imbalanced responses, combining pro- and anti-inflammatory outcomes. These findings confirm EVs as promising tools for therapeutic strategies to modulate mononuclear phagocyte functions in diverse pathological settings.