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.
Highlights
Sepsis is a syndrome of multiple life-threatening organ dysfunction caused by the dysregulated host response to infection (Singer et al, 2016)
The immune response initiated by invading pathogens failed to return homeostasis, which eventually leads to a pathological syndrome characterized by persistent excessive inflammation and immunosuppression
Monocyte Monocytes stimulated by Inflammation and infection release exosomes containing mitochondrial damage-associated molecular patterns, which reduce the chemotaxis and sterilization of neutrophils through TLR9 inhibition mediated by endosomal acidification (Itagaki et al, 2011; Konecna et al, 2021)
Summary
Sepsis is a syndrome of multiple life-threatening organ dysfunction caused by the dysregulated host response to infection (Singer et al, 2016). The immune response initiated by invading pathogens failed to return homeostasis, which eventually leads to a pathological syndrome characterized by persistent excessive inflammation and immunosuppression (van der Poll et al, 2017). The use of cytokines such as interleukin-7 (IL-7), interleukin-15 (IL-15), granulocytemacrophage colony-stimulating factor (GM-CSF) and co-inhibitory molecules blockade involving anti-programmed cell death receptor-1 (anti-PD-1) and anti-B and T lymphocyte attenuator (anti-BTLA) have been proven to reduce the mortality of sustained sepsis (Leentjens et al, 2013; Hutchins et al, 2014; Delano and Ward, 2016; van der Poll et al, 2017; Venet and Monneret, 2018; Steinhagen et al, 2020). We summarized the effects (activation or inhibition) and underlying mechanisms of exosomes of different origins (nonimmune and immune cells) and components on the immune system
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