Content area
Full text
Received Jan 3, 2018; Accepted Jan 29, 2018
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
1. Introduction
The incidence of sepsis is continuing to rise and accounts for approximately 215,000 deaths per year in the United States of America (USA) [1]. The management of sepsis places a large financial burden on health care systems with conservative estimates suggesting that the USA spends $17 billion treating sepsis annually [1–3].
Sepsis is a complex syndrome that has been defined as a life-threatening immune response to infection [4]. However, the pathogen load and its virulence and the subsequent host characteristics determine the extent and nature of this response [2, 5]. Neutrophils are one of the first lines of defense against invading pathogens and are responsible for containing and eliminating invading pathogens [6, 7]. Neutrophils are multifaceted innate immune cells that also modulate the inflammatory response and initiate the adaptive immune responses to sepsis via the release of cytokines. It is this coordinated response that maintains immune homeostasis [8].
In sepsis, there is a dysregulated immune response with activated circulating neutrophils releasing cytokines and reactive oxygen species (ROS) at sites distal to the infectious focus leading to multiorgan failure [7]. Additionally, neutrophils have been shown to demonstrate immunosuppressive phenotypes, with immaturity and altered chemokine expression responsible for some of these alterations [8]. This has pertinence in sepsis, with sepsis-induced immunosuppression being recognized as a clinical syndrome in survivors of sepsis, who have an increased susceptibility to nosocomial infections, frequent hospital readmissions, and subsequently increased late mortality [7, 9–11]. Recently, we described a reduction in systemic neutrophil migratory accuracy in lower respiratory tract infections, pneumonia, and a mild, ward-based pneumonia-associated sepsis cohort with evidence of prolonged migratory dysfunction after the septic event [12]. It is unclear whether reduced neutrophil migratory accuracy might also be a feature of a more severe sepsis cohort, how this might change over time, and whether other facets of neutrophil function might also be affected.
Following activation, triggered either by frustrated phagocytosis or sustained inflammation, neutrophils release neutrophil extracellular traps (NETs), whereby nuclear DNA laden with histones and granular contents are liberated into...