title: The role of neutrophils in immune dysfunction during severe inflammation.
abstract: Critically ill post-surgical, post-trauma and/or septic patients are characterised by severe inflammation. This immune response consists of both a pro- and an anti-inflammatory component. The pro-inflammatory component contributes to (multiple) organ failure whereas occurrence of immune paralysis predisposes to infections. Strikingly, infectious complications arise in these patients despite the presence of a clear neutrophilia. We propose that dysfunction of neutrophils potentially increases the susceptibility to infections or can result in the inability to clear existing infections. Under homeostatic conditions these effector cells of the innate immune system circulate in a quiescent state and serve as the first line of defence against invading pathogens. In severe inflammation, however, neutrophils are rapidly activated, which affects their functional capacities, such as chemotaxis, phagocytosis, intra-cellular killing, NETosis, and their capacity to modulate adaptive immunity. This review provides an overview of the current understanding of neutrophil dysfunction in severe inflammation. We will discuss the possible mechanisms of downregulation of anti-microbial function, suppression of adaptive immunity by neutrophils and the contribution of neutrophil subsets to immune paralysis.
authors.affiliation: Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. plelief2@umcutrecht.nl.|Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. plelief2@umcutrecht.nl.
authors.forename: Pieter H C
authors.initials: PH
authors.lastname: Leliefeld
authors.affiliation: Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Catharina M
authors.initials: CM
authors.lastname: Wessels
authors.affiliation: Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Luke P H
authors.initials: LP
authors.lastname: Leenen
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.|Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Leo
authors.initials: L
authors.lastname: Koenderman
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Anesthesiology and Critical Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Janesh
authors.initials: J
authors.lastname: Pillay
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D016638:Critical Illness / Q000401:mortality; D006801:Humans; D007154:Immune System Diseases / Q000175:diagnosis* / Q000209:etiology*; D007249:Inflammation / Q000150:complications / Q000276:immunology; D018375:Neutrophil Activation / Q000502:physiology*; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D018805:Sepsis / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents