Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Sepsis is a major health issue and a leading cause of death in hospitals globally. The treatment of sepsis is largely supportive, and there are no therapeutics available that target the underlying pathophysiology of the disease. The development of therapeutics for the treatment of sepsis is hindered by the heterogeneous nature of the disease. ⋯ However, there has been limited studies of immune cell function during sepsis and even fewer correlating omics and biomarker alterations to functional consequences. In this review, we will discuss how the heterogeneity of sepsis and associated immune cell phenotypes result from changes in the omic makeup of cells and its correlation with leukocyte dysfunction. We will also discuss how emerging techniques such as in silico modeling and machine learning can help in phenotyping sepsis patients leading to precision medicine.
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Injuries lead to an early systemic inflammatory state with innate immune system activation. Neutrophil extracellular traps (NETs) are a complex of chromatin and proteins released from the activated neutrophils. Although initially described as a response to bacterial infections, NETs have also been identified in the sterile postinjury inflammatory state. ⋯ Neutrophil extracellular trap formation and PAD activation have been shown to contribute to the postinjury inflammatory state leading to a detrimental effect on organ systems. This review describes our current understanding of the role of PAD and NET formation following injury and burn. This is a new field of study, and the emerging data appear promising for the future development of targeted biomarkers and therapies in trauma.
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Sepsis and trauma remain the leading causes of morbidity and mortality. Our understanding of the molecular pathogenesis in the development of multiple organ dysfunction in sepsis and trauma has evolved as more focus is on secondary injury from innate immunity, inflammation, and the potential role of endogenous danger molecules. Studies of the past several decades have generated evidence for extracellular RNAs (exRNAs) as biologically active mediators in health and disease. Here, we review studies on plasma exRNA profiling in mice and humans with sepsis and trauma, the role and mode of action by exRNAs, such as ex-micro(mi)RNAs, in host innate immune response, and their potential implications in various organ injury during sepsis and trauma.
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There is growing appreciation that skeletal muscle is a fully functional component of the body's innate immune system with the potential to actively participate in the host response to invading bacteria as opposed to being a passive target. In this regard, skeletal muscle in general and myocytes specifically possess an afferent limb that recognizes a wide variety of host pathogens via their interaction with multiple classes of cell membrane-bound and intracellular receptors, including toll-like receptors, cytokine receptors, NOD-like receptors, and the NLRP inflammasome. ⋯ Moreover, because there are important differences, this review focuses specifically on systemic infection and inflammation as opposed to the response of muscle to direct injury and various types of muscular dystrophies. To date, however, there are few definitive muscle-specific studies that are necessary to directly address the relative importance of muscle-derived immune activation as a contributor to either the systemic immune response or the local immune microenvironment within muscle during sepsis and the resultant downstream metabolic disturbances.
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Sepsis is a life-threatening organ dysfunction, caused by dysregulation of the host response to infection. To understand the underlying mechanisms of sepsis, the vast spectrum of extracellular vesicles (EVs) is gaining importance in this research field. A connection between EVs and sepsis was shown in 1998 in an endotoxemia pig model. ⋯ Extracellular vesicles of different cellular origin, such as leucocytes, macrophages, platelets, and granulocytes, have been suggested as potential sepsis biomarkers. They ensure the diagnosis of sepsis earlier than classical clinical inflammation markers, such as C-reactive protein, leucocytes, or IL-6. This review summarizes the three roles of EVs in sepsis-mediator/inducer, biomarker, and therapeutic tool.