Impact of extracellular vesicles on innate immunity

Abstract

Purpose of reviewExtracellular vesicles released by prokaryote or eukaryote cells are emerging as mechanisms of cell-to-cell communication, by either physically interacting with the surface of target cells or transferring proteins/ peptides, lipids, carbohydrates, and nuclei acids to acceptor cells. Accumulating evidence indicates that extracellular vesicles, among other functions, regulate innate and adaptive immune responses. We revisit here the effects that extracellular vesicles of various origins have on innate immunity. Recent findingsExtracellular vesicles comprise a heterogeneous group of vesicles with different biogenesis, composition and biological properties, which include exosomes, microvesicles, apoptotic cell-derived extracellular vesicles, and other extracellular vesicles still not well characterized. Extracellular vesicles released by pathogens, leukocytes, nonhematopoietic cells, tumor cells, and likely allografts, can either stimulate or suppress innate immunity via multiple mechanisms. These include transfer to target leukocytes of proinflammatory or anti-inflammatory mediators, membrane receptors, enzymes, mRNAs, and noncoding RNAs; and interaction of extracellular vesicles with the complement and coagulation systems. As a result, extracellular vesicles affect differentiation, polarization, activation, tissue recruitment, cytokine and chemokine production, cytolytic and phagocytic function, and antigen transfer ability, of different types of innate immune cells.

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“…In case of intramuscular [ 41 ] as well as cutaneous [ 42 ] administration, directly transfected cells may express the antigen. Antigen may be transferred to regional APC by the release of exosomes [ 43 ] or apoptotic bodies [ 44 ]. In either case, antigen of exogenous origin is presented largely on MHCII, resulting in the activation of antigen-specific CD4 + T helper cells (Th) [ 45 ].…”

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“…Over the last decades, exosomes have been described to play emerging roles in a number of physiological or regenerative processes, infection and disease; therefore, they have been largely investigated in biomedical research, due to their potential applications in cell-based therapy, diagnostics, and drug delivery, among others (reviewed in Reference [ 25 ]). Exosomes offer a potent mechanism for communication between nearby or distant cells or tissues, to change their physiological functions and properties in particular innate and adaptive immune responses [ 26 ]. In mammals, exosomes participate in responses during viral and bacterial infection, in a complex interplay between pathogens and different types of immune cells of the host (macrophages, NK cells, DCs, T and B cells).…”

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“…Exosomes are directly involved in immune signaling in as much as they can cargo pro-inflammatory and anti-inflammatory cytokines to target cells [ 42 – 45 ] as well as stimulate the secretion of these cytokines from recipient cells [ 35 , 46 , 47 ] . For instance, a recent study documented the role of apoptotic exosome-like vesicles in promoting the synthesis of the pro-inflammatory IL-1β in macrophages, thereby contributing to their activation [ 48 ] .…”

“…For instance, a recent study documented the role of apoptotic exosome-like vesicles in promoting the synthesis of the pro-inflammatory IL-1β in macrophages, thereby contributing to their activation [ 48 ] . In contrast, exosomes have also been shown to promote the production of the anti-inflammatory transforming growth factor-β (TGF-β) in macrophages leading to the inhibition of the innate immune response [ 47 , 49 ] . Murine LPS-stimulated macrophages produce exosomes containing endoplasmic reticulum aminopeptidase 1, TNF-α, IFN-γ, and CCL3, which induces phagocytosis and nitric oxide synthesis in adjacent recipient macrophages [ 47 , 50 ] , important cellular mediators in clearing the microbial infection.…”

“…In contrast, exosomes have also been shown to promote the production of the anti-inflammatory transforming growth factor-β (TGF-β) in macrophages leading to the inhibition of the innate immune response [ 47 , 49 ] . Murine LPS-stimulated macrophages produce exosomes containing endoplasmic reticulum aminopeptidase 1, TNF-α, IFN-γ, and CCL3, which induces phagocytosis and nitric oxide synthesis in adjacent recipient macrophages [ 47 , 50 ] , important cellular mediators in clearing the microbial infection. Additionally, epithelial cell uptake of exosomes secreted by LPS-induced dendritic cells (DCs) has been shown to stimulate their activation and subsequent release of cytokines and chemokines to further the innate response [ 51 , 52 ] .…”