scholarly journals Neutrophil Extracellular Traps in the Second Decade

2018 ◽  
Vol 10 (5-6) ◽  
pp. 414-421 ◽  
Author(s):  
Volker Brinkmann
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Pathophysiological Mechanisms ◽  
Extracellular Traps ◽  
Concise Overview ◽  
Health And Disease ◽  
The Right

Nearly 15 years after the first description of neutrophil extracellular traps (NETs), our knowledge concerning this structure has expanded considerably. Initially, NETs were considered solely an elaborate function of the innate immune system to combat invading microorganisms. Successively it became clear that NETs have farther-reaching capabilities. They are involved in a series of pathophysiological mechanisms ranging from inflammation to thrombosis where they fulfill essential functions when produced at the right site and the right time but can have a serious impact when generation or clearance of NETs is inadequately controlled. This review provides a concise overview on the far-reaching functions of NETs in health and disease.

scholarly journals Neutrophil extracellular traps and their role in health and disease

2016 ◽  
Vol Volume 112 (Number 1/2) ◽  
Author(s):  
Jan G. Nel ◽  
Annette J. Theron ◽  
Roger Pool ◽  
Chrisna Durandt ◽  
Gregory R. Tintinger ◽  
...  
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Neutrophil Extracellular Traps ◽  
Limited Range ◽  
Innate Immune ◽  
Microbial Pathogens ◽  
Alternative Mechanism ◽  
Viral Pathogens ◽  
Extracellular Traps ◽  
Health And Disease

Abstract The human innate immune system is indispensable for protection against potentially invasive microbial and viral pathogens, either neutralising them or containing their spread until effective mobilisation of the slower, adaptive (specific), immune response. Until fairly recently, it was believed that the human innate immune system possessed minimal discriminatory activity in the setting of a rather limited range of microbicidal or virucidal mechanisms. However, recent discoveries have revealed that the innate immune system possesses an array of novel pathogen recognition mechanisms, as well as a resourceful and effective alternative mechanism of phagocyte (predominantly neutrophil)-mediated, anti-infective activity known as NETosis. The process of NETosis involves an unusual type of programmed, purposeful cell death, resulting in the extracellular release of a web of chromatin heavily impregnated with antimicrobial proteins. These structures, known as neutrophil extracellular traps (NETs), immobilise and contribute to the eradication of microbial pathogens, ensuring that the anti-infective potential of neutrophils is sustained beyond the lifespan of these cells. The current review is focused on the mechanisms of NETosis and the role of this process in host defence. Other topics reviewed include the potential threats to human health posed by poorly controlled, excessive formation of NETs, specifically in relation to development of autoimmune and cardiovascular diseases, as well as exacerbation of acute and chronic inflammatory disorders of the airways.

Role of Toll-like receptors in liver health and disease

2011 ◽  
Vol 121 (10) ◽  
pp. 415-426 ◽  
Author(s):  
Ruth Broering ◽  
Mengji Lu ◽  
Joerg F. Schlaak
Keyword(s):  
Immune System ◽  
Liver Disease ◽  
Innate Immune System ◽  
Innate Immune ◽  
Toll Like Receptors ◽  
Evolutionarily Conserved ◽  
Liver Health ◽  
Health And Disease ◽  
Molecular Patterns

TLRs (Toll-like receptors), as evolutionarily conserved germline-encoded pattern recognition receptors, have a crucial role in early host defence by recognizing so-called PAMPs (pathogen-associated molecular patterns) and may serve as an important link between innate and adaptive immunity. In the liver, TLRs play an important role in the wound healing and regeneration processes, but they are also involved in the pathogenesis and progression of various inflammatory liver diseases, including autoimmune liver disease, alcoholic liver disease, non-alcoholic steatohepatitis, fibrogenesis, and chronic HBV (hepatitis B virus) and HCV (hepatitis C virus) infection. Hepatitis viruses have developed different evading strategies to subvert the innate immune system. Thus recent studies have suggested that TLR-based therapies may represent a promising approach in the treatment in viral hepatitis. The present review focuses on the role of the local innate immune system, and TLRs in particular, in the liver.

scholarly journals Immune System Disequilibrium—Neutrophils, Their Extracellular Traps, and COVID-19-Induced Sepsis

2021 ◽  
Vol 8 ◽  
Author(s):  
Colm Keane ◽  
Matthew Coalter ◽  
Ignacio Martin-Loeches
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Innate Immune ◽  
Organ Injury ◽  
Stem Cell Therapies ◽  
Cell Therapies ◽  
Adaptive Immune ◽  
Extracellular Traps ◽  
Adaptive Immune Cells ◽  
Induced Apoptosis

Equilibrium within the immune system can often determine the fate of its host. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic. Immune dysregulation remains one of the main pathophysiological components of SARS-CoV-2-associated organ injury, with over-activation of the innate immune system, and induced apoptosis of adaptive immune cells. Here, we provide an overview of the innate immune system, both in general and relating to COVID-19. We specifically discuss “NETosis,” the process of neutrophil release of their extracellular traps, which may be a more recently described form of cell death that is different from apoptosis, and how this may propagate organ dysfunction in COVID-19. We complete this review by discussing Stem Cell Therapies in COVID-19 and emerging COVID-19 phenotypes, which may allow for more targeted therapy in the future. Finally, we consider the array of potential therapeutic targets in COVID-19, and associated therapeutics.

scholarly journals Comparative analysis of neutrophil and monocyte epigenomes

2017 ◽  
Author(s):  
Daniel Rico ◽  
Joost HA Martens ◽  
Kate Downes ◽  
Enrique Carrillo-de-Santa-Pau ◽  
Vera Pancaldi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune System ◽  
Innate Immune System ◽  
Regulatory Elements ◽  
Innate Immune ◽  
Human Neutrophils ◽  
Integrated Analysis ◽  
Differentiation Potential ◽  
Differentiated Cells ◽  
Health And Disease

ABSTRACTNeutrophils and monocytes provide a first line of defense against infections as part of the innate immune system. Here we report the integrated analysis of transcriptomic and epigenetic landscapes for circulating monocytes and neutrophils with the aim to enable downstream interpretation and functional validation of key regulatory elements in health and disease. We collected RNA-seq data, ChIP-seq of six histone modifications and of DNA methylation by bisulfite sequencing at base pair resolution from up to 6 individuals per cell type. Chromatin segmentation analyses suggested that monocytes have a higher number of cell-specific enhancer regions (4-fold) compared to neutrophils. This highly plastic epigenome is likely indicative of the greater differentiation potential of monocytes into macrophages, dendritic cells and osteoclasts. In contrast, most of the neutrophil-specific features tend to be characterized by repressed chromatin, reflective of their status as terminally differentiated cells. Enhancers were the regions where most of differences in DNA methylation between cells were observed, with monocyte-specific enhancers being generally hypomethylated. Monocytes show a substantially higher gene expression levels than neutrophils, in line with epigenomic analysis revealing that gene more active elements in monocytes. Our analyses suggest that the overexpression of c-Myc in monocytes and its binding to monocyte-specific enhancers could be an important contributor to these differences. Altogether, our study provides a comprehensive epigenetic chart of chromatin states in primary human neutrophils and monocytes, thus providing a valuable resource for studying the regulation of the human innate immune system.

scholarly journals Neutrophils and NETs in modulating acute and chronic inflammation

Blood ◽  
2019 ◽  
Vol 133 (20) ◽  
pp. 2178-2185 ◽  
Author(s):  
Fernanda V. S. Castanheira ◽  
Paul Kubes
Keyword(s):  
Chronic Inflammation ◽  
Host Defense ◽  
Innate Immune System ◽  
Tissue Repair ◽  
Essential Role ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Extracellular Traps ◽  
Acute And Chronic Inflammation

Abstract Neutrophils are an absolutely essential part of the innate immune system, playing an essential role in the control of infectious diseases but more recently are also being viewed as important players in tissue repair. Neutrophils are able to counteract an infection through phagocytosis and/or the release of neutrophil extracellular traps (NETs). By contrast, neutrophils help repair damaged tissues, limiting NET production but still phagocytosing debris. However, when inflammation is recurrent, or the inciting agent persists, neutrophils through a frustrated inability to resolve the problem can release NETs to exacerbate tissue damage during inappropriate inflammation. In this review, we discuss the mechanisms of NET formation, as well as the apparent paradoxical role of neutrophils and NETs in host defense, chronic inflammation, and tissue disrepair.

scholarly journals The Dual Role of Myeloperoxidase in Immune Response

2020 ◽  
Vol 21 (21) ◽  
pp. 8057 ◽  
Author(s):  
Jürgen Arnhold
Keyword(s):  
Immune Response ◽  
Innate Immune System ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Major Constituent ◽  
Extracellular Traps ◽  
Atherosclerotic Lesions ◽  
Disease Specific ◽  
Frustrated Phagocytosis

The heme protein myeloperoxidase (MPO) is a major constituent of neutrophils. As a key mediator of the innate immune system, neutrophils are rapidly recruited to inflammatory sites, where they recognize, phagocytose, and inactivate foreign microorganisms. In the newly formed phagosomes, MPO is involved in the creation and maintenance of an alkaline milieu, which is optimal in combatting microbes. Myeloperoxidase is also a key component in neutrophil extracellular traps. These helpful properties are contrasted by the release of MPO and other neutrophil constituents from necrotic cells or as a result of frustrated phagocytosis. Although MPO is inactivated by the plasma protein ceruloplasmin, it can interact with negatively charged components of serum and the extracellular matrix. In cardiovascular diseases and many other disease scenarios, active MPO and MPO-modified targets are present in atherosclerotic lesions and other disease-specific locations. This implies an involvement of neutrophils, MPO, and other neutrophil products in pathogenesis mechanisms. This review critically reflects on the beneficial and harmful functions of MPO against the background of immune response.

scholarly journals Olfactomedin 4 marks a subset of neutrophils in mice

2018 ◽  
Vol 25 (1) ◽  
pp. 22-33 ◽  
Author(s):  
Matthew N Alder ◽  
Jaya Mallela ◽  
Amy M Opoka ◽  
Patrick Lahni ◽  
David A Hildeman ◽  
...  
Keyword(s):  
Innate Immune System ◽  
Immune Cell ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Human Neutrophils ◽  
Null Mouse ◽  
Immune Functions ◽  
Single Population ◽  
Extracellular Traps ◽  
Neutrophil Differentiation

Neutrophils are the most abundant immune cell of the innate immune system and participate in essential immune functions. Heterogeneity within neutrophils has been documented, but it is difficult to distinguish if these are altered activation states of a single population or separate subpopulations of neutrophils determined at the time of differentiation. Several groups have identified a subset of human neutrophils that express olfactomedin 4 (OLFM4) and increased OLFM4+ neutrophils during sepsis is correlated with worse outcome, suggesting these neutrophils or the OLFM4 they secrete may be pathogenic. We tested if mice could be used as a model to study OLFM4+ neutrophils. We found the OLFM4 expressing subset of neutrophils is conserved in mice. Depending on the strain, 7–35% of murine neutrophils express OLFM4 and expression is determined early in neutrophil differentiation. OLFM4+ neutrophils phagocytose and transmigrate with similar efficiency as OLFM4− neutrophils. Here we show that within neutrophil extracellular traps (NETs) OLFM4+ and OLFM4− neutrophils undergo NETosis and OLFM4 colocalizes. Finally, we generated an OLFM4 null mouse and show that these mice are protected from death when challenged with sepsis, providing further evidence that the OLFM4 expressing subpopulation of neutrophils, or the OLFM4 they secrete, may be pathogenic during overwhelming infection.

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