NEUTROPHIL HETEROGENEITY IN SEPSIS: THE ROLE OF DAMAGE-ASSOCIATED MOLECULAR PATTERNS.

Abstract

Sepsis is a severe inflammatory disease syndrome caused by the dysregulated host response to infection. Neutrophils act as the first line of defense against pathogens by releasing effector molecules such as reactive oxygen species, myeloperoxidase, and neutrophil extracellular traps. However, uncontrolled activation of neutrophils and extensive release of effector molecules often cause a "friendly fire" to damage organ systems. Although neutrophils are considered a short-lived, terminally differentiated homogeneous population, recent studies have revealed its heterogeneity comprising different subsets or states implicated in sepsis pathophysiology. Besides the well-known N1 and N2 subsets of neutrophils, several new subsets including aged, antigen-presenting, reverse-migrated, intercellular adhesion molecule-1 + , low-density, olfactomedin 4 + , and Siglec-F + neutrophils have been reported. These neutrophils potentially contribute to the pathogenesis of sepsis based on their proinflammatory and immunosuppressive functions. Damage-associated molecular patterns (DAMPs) are endogenous molecules to induce inflammation by stimulating pattern recognition receptors on immune cells. Different kinds of DAMPs have been shown to contribute to sepsis pathophysiology, including extracellular cold-inducible RNA-binding protein, high-mobility group box 1, extracellular histones, and heat shock proteins. In this review, we summarize the different subsets of neutrophils and their association with sepsis and discuss the novel roles of DAMPs on neutrophil heterogeneity.