Innate Immunity Communicates Using the Language of Extracellular Microvesicles

Abstract

The innate immunity system and extracellular microvesicles (ExMVs) both emerged early in the evolution of life, which is why its innate immunity cellular arm and its soluble-component arm learned, understood, and adapted to the “language” of ExMVs. This was most likely the first language of cell–cell communication during evolution, which existed before more specific intercellular crosstalk involving specific ligands and receptors emerged. ExMVs are involved in several processes in the body, including immune and coagulation responses, which are part of inflammation. In this review we will briefly highlight what is known about how ExMVs regulate the function of the cellular arm of innate immunity, including macrophages, monocytes, granulocytes, natural killer cells, and dendritic cells, and affect the soluble components of this system, which consists of the complement cascade (ComC) and soluble, circulating, pattern-recognition receptors (collectins, ficolins, and pentaxrins). These effects are direct, due to the fact that ExMVs affect the biological functions of innate immunity cells and may directly interact with soluble components of this system. Moreover, by activating coagulation proteases, ExMVs may also indirectly activate the ComC. In this review, we will use the term “extracellular microvesicles” (ExMVs) to refer to these small, spheroidal blebs of different sizes, which are surrounded by a membrane lipid layer. We will focus on the role of both ExMVs released during cell-surface membrane budding and smaller ExMVs, known as exosomes, which are derived from the budding of the endosomal membrane compartment. Finally, we will provide a brief update on the potential therapeutic applications of ExMVs, with a special emphasis on innate immunity. Graphical Abstract

Nanomaterial Exposure, Extracellular Vesicle Biogenesis and Adverse Cellular Outcomes: A Scoping Review

“…This study focused on research that demonstrated a potential relationship of EV secretion induced by NMs. EVs are now recognized as an important pathway for intercellular communication by exchanging various types of payloads between cells [ 21 ]. While the cellular transfer of NMs and their payloads has received increasing attention, the role of EVs in this process remains elusive.…”

“…The inhibition or stimulation of EV secretion in response to external stimuli can cause alterations in cell communication and result in substantial implications to cell/tissue dysfunction and ultimately pathological consequences [ 14 , 17 , 19 ]. Emerging evidence suggests that the NM exposure of cells and organs stimulates the secretion and disturbs EV biogenesis by activating various biological processes that include immune-system activation, toxicity reduction mediated by exocytosis of NMs through EVs, and the induction of pro-thrombotic effects in cardiovascular and metabolic diseases [ 20 , 21 , 22 , 23 , 24 , 25 ]. Interestingly, EVs have demonstrated the importance of explaining the possible outcomes of many physiological processes, including the cytotoxic and inflammatory processes induced by NMs [ 10 , 20 , 26 ].…”

A systematic review and Meta-analysis of urinary extracellular vesicles proteome in diabetic nephropathy

“…The density of urinary EV of DN patients were siginificantly reduced compared with T1DM ( 13 ). However, EV secretion mechanisms remove harmful substance from the plasma membrane, ensuring intracellular environmental balance ( 52 ). The substant reduces EV release, and crosstalk between cells about biogenesis and autophagy contributes to maintaining cellular homeostasis under external and internal stresses, leading to chronic kidney disease dysfunction ( 53 ).…”

“…EV regulate the gene expression and signaling pathways of target cells by participating in antigen presentation, transmission of antigenic peptides or immunomodulatory molecules, and regulate adaptive immune response and innate immune response ( 6 ). The membrane attack complex C5b-C9 can be removed from the plasma membrane by exosome secretion and excretion mechanisms, ensuring cell survival and recovery from a large number of complement attacks ( 52 ). Besides that, the C1q protein binds to the surface of the EV by electrostatic action, and further to the combined with immunoglobulin, triggering the classical pathway of complement cascade activation and triggering the deposition of C3 and C4.…”

Prostasomes (Exosomes) Mediate Functional Abilities to Recipient Cells through Transfer of Proteins and Nucleic Acids: A Comprehensive Model for Exosomal Intercellular Communication

“…Cancer cell derived exosomes promote formation of metastases by initiating epithelial-mesenchymal-transition (EMT) within the tumor microenvironment. They will also travel to distant places (even passing the blood brain barrier) via various interstitial fluids in the extracellular space and be selectively taken up and induce transformation of normal cells into malignant cells [40][41][42][43][44].…”