The role of extracellular vesicles when innate meets adaptive

Abstract

Innate immune cells are recognized for their rapid and critical contribution to the body’s first line of defense against invading pathogens and harmful agents. These actions can be further amplified by specific adaptive immune responses adapted to the activating stimulus. Recently, the awareness has grown that virtually all innate immune cells, i.e., mast cells, neutrophils, macrophages, eosinophils, basophils, and NK cells, are able to communicate with dendritic cells (DCs) and/or T and B cells, and thereby significantly contribute to the orchestration of adaptive immune responses. The means of communication that are thus far primarily associated with this function are cell-cell contacts and the release of a broad range of soluble mediators. Moreover, the possible contribution of innate immune cell-derived extracellular vesicles (EVs) to the modulation of adaptive immunity will be outlined in this review. EVs are submicron particles composed of a lipid bilayer, proteins, and nucleic acids released by cells in a regulated fashion. EVs are involved in intercellular communication between multiple cell types, including those of the immune system. A good understanding of the mechanisms by which innate immune cell-derived EVs influence adaptive immune responses, or vice versa, may reveal novel insights in the regulation of the immune system and can open up new possibilities for EVs (or their components) in controlling immune responses, either as a therapy, target, or as an adjuvant in future immune modulating treatments.

Neutrophil exosomes enhance the skin autoinflammation in generalized pustular psoriasis via activating keratinocytes

“…In wound healing, neutrophil microparticles impede actin dynamics, cell spreading, and cell-cycle arrest in intestinal epithelial cells via delivering active myeloperoxidase (24). In short, neutrophil vesicles, including exosomes, can deliver information to recipient cells, potentially exerting fundamental effects in a variety of inflammations and cancers (25).…”

Embryonic extracellular vesicles as informers to the immune cells at the maternal–fetal interface

“…Similarly, mast cells can excrete EVs with a proinflammatory role favouring the maturation and migration of immune cells such as DC, while EVs released by neutrophils are more probably associated with suppression signals [14]. Their modulation occurs in order to stimulate or suppress the response depending on the receptors carried by the EV membrane and the chemical mediators in their content, such as cytokines and chemokines.…”

“…The enhancement of the inflammatory signals can take place through interleukin (IL)-1 carried by EVs, which are typically released from monocytes or through platelet-activating factor (PAF, 1-o-alkyl-2-acetylsn-glyc-ero-3-phosphocholine), IL-1β and caspase-1 from EVs detached from platelets, macrophages and dendritic cells (DC). Similarly, mast cells can excrete EVs with a proinflammatory role favouring the maturation and migration of immune cells such as DC, while EVs released by neutrophils are more probably associated with suppression signals [14]. Exosomes can even carry preformed antigen-peptide/major histocompatibility complexes (pMHCs) directly from peripheral infected or neoplastic cells to antigen-presenting cells (APCs).…”

Extracellular Vesicles as Mediators of Cellular Crosstalk Between Immune System and Kidney Graft

“…IRI triggers a complex, alloantigen-independent immune response characterized by crosstalk between PMNs, macrophages, and DCs (123). All these cells release EVs with pro-inflammatory and anti-inflammatory effects (see above) (19). Two other cell types release critical EVs in this condition: endothelial cells and renal tubular epithelial cells.…”

“…EVs released from innate immune cells, such as macrophages, dendritic cells (DCs), or natural killer (NK) cells, are involved in the regulation of innate immune response mainly as proinflammatory and paracrine mediators (4,19). However, their immunomodulatory role is probably far more complex and includes anti-inflammatory and immunosuppressive effects.…”