DAMPs and NETs in Sepsis.

Naomi-Liza Denning,Steven D Gurien,Monowar Aziz,Ping Wang

doi:10.3389/fimmu.2019.02536

Abstract

Sepsis is a deadly inflammatory syndrome caused by an exaggerated immune response to infection. Much has been focused on host response to pathogens mediated through the interaction of pathogen-associated molecular patterns (PAMPs) and pattern recognition receptors (PRRs). PRRs are also activated by host nuclear, mitochondrial, and cytosolic proteins, known as damage-associated molecular patterns (DAMPs) that are released from cells during sepsis. Some well described members of the DAMP family are extracellular cold-inducible RNA-binding protein (eCIRP), high mobility group box 1 (HMGB1), histones, and adenosine triphosphate (ATP). DAMPs are released from the cell through inflammasome activation or passively following cell death. Similarly, neutrophil extracellular traps (NETs) are released from neutrophils during inflammation. NETs are webs of extracellular DNA decorated with histones, myeloperoxidase, and elastase. Although NETs contribute to pathogen clearance, excessive NET formation promotes inflammation and tissue damage in sepsis. Here, we review DAMPs and NETs and their crosstalk in sepsis with respect to their sources, activation, release, and function. A clear grasp of DAMPs, NETs and their interaction is crucial for the understanding of the pathophysiology of sepsis and for the development of novel sepsis therapeutics.

Highlights

Sepsis is common and deadly; 30–50% of patients suffering an in-hospital mortality have sepsis
We focus on damage-associated molecular patterns (DAMPs), neutrophil extracellular traps (NETs), and explore their interplay during sepsis (Figure 1)
Numerous endogenous molecules have been identified as inflammation-causing DAMPs, here we briefly review a selective group of DAMPs which have been strongly implicated in sepsis

Summary

Introduction

Sepsis is common and deadly; 30–50% of patients suffering an in-hospital mortality have sepsis. DAMPs are host nuclear or cytoplasmic non-microbial molecules which, when released from the cell following tissue injury, serve as potent activators of the immune system initiating and perpetuating a non-infectious inflammatory response to cause systemic inflammation, organ injury, and death [8,9,10]. Activated neutrophils produce reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), and NETs which contain noxious molecules, leading to tissue inflammation and injury in sepsis.

Results

Conclusion