Exosome: The Regulator of the Immune System in Sepsis

Abstract

Sepsis is a syndrome comprised of a series of life-threatening organ dysfunctions caused by a maladjusted body response to infection with no effective treatment. There is growing evidence that the immune system plays a core role in sepsis. Pathogens cause abnormal host immune response and eventually lead to immunosuppression, which is an important cause of death in patients with sepsis. Exosomes are vesicles derived from double invagination of plasma membrane, associating with immune responses closely. The cargos delivered by exosomes into recipient cells, especially immune cells, effectively alter their response and functions in sepsis. In this review, we focus on the effects and mechanisms of exosomes on multiple immune cells, as well as the role of immune cell-derived exosomes in sepsis. This is helpful for us to have an in-depth understanding of the mechanism of immune disorders in sepsis. Exosomes is also expected to become a novel target and therapeutic approach for sepsis.

The Concentration of Large Extracellular Vesicles Differentiates Early Septic Shock From Infection

“…Our study found that, in septic shock patients, most plasma-derived EVs are of non-leukocyte origins (i.e., platelet-EVs, erythrocyte-EVs, endothelial cells-EVs; ranked in descending order of plasma concentration). Interestingly, neutrophil-derived EVs only constitute a minority of plasma EVs despite the existing sepsis and infection-induced neutrophil dysfunctions ( 10 ) and previous publications highlighting the association between neutrophil EVs and the inflammatory process of sepsis ( 26 , 27 ). These findings emphasize an important role of blood cells of non-leukocyte origin in modulating and propagating the hyperinflammatory reactions of sepsis and infection.…”

“…A quest to seek the signature biomarkers of sepsis is still ongoing; EV characterization, either by their cell origins, specific surface markers, or their miRNA contents, is an area that has been receiving interest in this matter. Numerous EV subtypes were linked to various aspects of sepsis pathobiology ( 26 ); some of them promotes the inflammatory reactions of sepsis ( 27 – 32 ) while others alleviate the damage from sepsis ( 33 – 38 ). Our study found that, in septic shock patients, most plasma-derived EVs are of non-leukocyte origins (i.e., platelet-EVs, erythrocyte-EVs, endothelial cells-EVs; ranked in descending order of plasma concentration).…”

Potential Application of Exosomes in Vaccine Development and Delivery

“…Our literature review suggests that stress-evoked cytokines and chemokines can both facilitate host survival and endanger our health. Recent studies confirm that exosomes play a vital role in reducing the content of immune inhibitory mRNA and immune stimulatory damage-associated molecular patterns (DAMPs) from systemic circulation (253). Thus, circulating exosomes play a fundamental role in immune homeostasis during stress conditions and vice versa, depending on cellular conditions.…”

Exosomes: Potential Disease Biomarkers and New Therapeutic Targets

“…Exosomes have also become an important target and focus for the sepsis treatment [280]. For example, miR-27b loaded on MSC-derived exosomes inhibit the development of sepsis by regulating Histone demethylase Jumonji D3 and inactivating the nuclear factor κB (NF-κB) signaling pathway, thereby decreasing the production of proinflammatory cytokines [267].…”