Pathological alteration and therapeutic implications of sepsis-induced immune cell apoptosis

Abstract

Sepsis is a life-threatening organ dysfunction syndrome caused by dysregulated host response to infection that leads to uncontrolled inflammatory response followed by immunosuppression. However, despite the high mortality rate, no specific treatment modality or drugs with high efficacy is available for sepsis to date. Although improved treatment strategies have increased the survival rate during the initial state of excessive inflammatory response, recent trends in sepsis show that mortality occurs at a period of continuous immunosuppressive state in which patients succumb to secondary infections within a few weeks or months due to post-sepsis “immune paralysis.” Immune cell alteration induced by uncontrolled apoptosis has been considered a major cause of significant immunosuppression. Particularly, apoptosis of lymphocytes, including innate immune cells and adaptive immune cells, is associated with a higher risk of secondary infections and poor outcomes. Multiple postmortem studies have confirmed that sepsis-induced immune cell apoptosis occurs in all age groups, including neonates, pediatric, and adult patients, and it is considered to be a primary contributing factor to the immunosuppressive pathophysiology of sepsis. Therapeutic perspectives targeting apoptosis through various strategies could improve survival in sepsis. In this review article, we will focus on describing the major apoptosis process of immune cells with respect to physiologic and molecular mechanisms. Further, advances in apoptosis-targeted treatment modalities for sepsis will also be discussed.

TICAM2-related pathway mediates neutrophil exhaustion

“…Despite the advancement of critical care and supportive therapies 51 , the incidence of sepsis remains high, with ~ 30 million people worldwide being affected and ~ 6 million deaths annually 52 , due to the lack of effective cure. The progression of sepsis is correlated with the dysregulation of innate immune cells including neutrophils, with neutrophil dysfunction and/or exhaustion leading to elevated mortality and morbidity post sepsis 53 .…”

Marine Algal Antioxidants as Potential Vectors for Controlling Viral Diseases

“…The 85% of critically ill patients with COVID-19 showed leukocytosis, high levels of monocytes and neutrophils, and lymphopenia [19], which is a lack of lymphocytes, with patients dying with comorbidity and high levels of plasma cytokines [20]. Lymphopenia and hypercytokinemia are directly correlated with increased severity, mortality and a dysregulated immunological response [21]. First epidemiological indications reveal that the COVID-19 patients requiring intensive care are older and are more likely to have hypertension, diabetes, cardiovascular or cerebrovascular pathologies [22].…”

Peptidylarginine deiminase 2 has potential as both a biomarker and therapeutic target of sepsis

“…NETosis sequesters bacteria for pathogen inactivation ( 3 ), and pyroptosis is an antimicrobial response that mainly takes place in macrophages. Although uncontrolled immune cell death has recently been considered as a significant contributing factor to sepsis pathogenesis ( 4 – 6 ), it is presently unknown whether manipulation of the regulation of NETosis and/or pyroptosis influences sepsis progression.…”