Macrophage Extracellular Traps: A Scoping Review

Doster, Ryan S.; Rogers, Lisa M.; Gaddy, Jennifer A.; Aronoff, David M.

doi:10.1159/000480373

Cited by 185 publications

(164 citation statements)

References 60 publications

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“…Since extracellular traps are not produced exclusively by neutrophils, being also produced by mononuclear cells, termed monocyte or macrophage extracellular traps (METs) [52,53], we calculated the proportions of polynuclear and mononuclear cells in the NET-positive samples. It proved to be specifically the polynuclear cells, rather than the cause of the pleocytosis (i.e., the diagnosis), that correlated with the levels of NETs.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil Extracellular Traps (NETs) in the Cerebrospinal Fluid Samples from Children and Adults with Central Nervous System Infections

Söderberg

Enocsson

Skogman

et al. 2019

Cells

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Neutrophils operate as part of the innate defence in the skin and may eliminate the Borrelia spirochaete via phagocytosis, oxidative bursts, and hydrolytic enzymes. However, their importance in Lyme neuroborreliosis (LNB) is unclear. Neutrophil extracellular trap (NET) formation, which is associated with the production of reactive oxygen species, involves the extrusion of the neutrophil DNA to form traps that incapacitate bacteria and immobilise viruses. Meanwhile, NET formation has recently been studied in pneumococcal meningitis, the role of NETs in other central nervous system (CNS) infections has previously not been studied. Here, cerebrospinal fluid (CSF) samples from clinically well-characterised children (N = 111) and adults (N = 64) with LNB and other CNS infections were analysed for NETs (DNA/myeloperoxidase complexes) and elastase activity. NETs were detected more frequently in the children than the adults (p = 0.01). NET presence was associated with higher CSF levels of CXCL1 (p < 0.001), CXCL6 (p = 0.007), CXCL8 (p = 0.003), CXCL10 (p < 0.001), MMP-9 (p = 0.002), TNF (p = 0.02), IL-6 (p < 0.001), and IL-17A (p = 0.03). NETs were associated with fever (p = 0.002) and correlated with polynuclear pleocytosis (r s = 0.53, p < 0.0001). We show that neutrophil activation and active NET formation occur in the CSF samples of children and adults with CNS infections, mainly caused by Borrelia and neurotropic viruses. The role of NETs in the early phase of viral/bacterial CNS infections warrants further investigation. supervision, C.S., D.N. and L.E.M.; project administration, J.S.; funding, D.A., B.H.S., D.N., L.E.M. and C.S.; acquisition, D.A., L.E.M., C.S. and J.S. All authors have read and agreed to the published version of the manuscript.

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Section: Discussionmentioning

confidence: 99%

Neutrophil Extracellular Traps (NETs) in the Cerebrospinal Fluid Samples from Children and Adults with Central Nervous System Infections

Söderberg

Enocsson

Skogman

et al. 2019

Cells

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“…The DNA and histone protein components of NETs are their major players in host defense and inflammation . The stressful conditions causing the death of innate immune cells (neutrophils, monocytes, and eosinophils) release extracellular traps (NETs, Mϕ extracellular traps, and eosinophil extracellular traps) along with the release of both mitochondrial and nuclear DNA into the extracellular environment . The extracellular DNA generates the primary B cell‐mediated IgG1 Ab, canonical Th2 type immune, and a peripheral effector response via IRF‐3 signaling .…”

Section: Cgas‐sting Signaling In Autoinflammation and Autoimmunitymentioning

confidence: 99%

A STING to inflammation and autoimmunity

Kumar

2019

Journal of Leukocyte Biology

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Various intracellular pattern recognition receptors (PRRs) recognize cytosolic pathogenassociated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Cyclic GMP-AMP synthase (cGAS), a cytosolic PRR, recognizes cytosolic nucleic acids including dsDNAs. The recognition of dsDNA by cGAS generates cyclic GMP-AMP (GAMP). The cGAMP is then recognized by STING generating type 1 IFNs and NF-B-mediated generation of proinflammatory cytokines and molecules. Thus, cGAS-STING signaling mediated recognition of cytosolic dsDNA causing the induction of type 1 IFNs plays a crucial role in innate immunity against cytosolic pathogens, PAMPs, and DAMPs. The overactivation of this system may lead to the development of autoinflammation and autoimmune diseases. The article opens with the introduction of different PRRs involved in the intracellular recognition of dsDNA and gives a brief introduction of cGAS-STING signaling. The second section briefly describes cGAS as intracellular PRR required to recognize intracellular nucleic acids (dsDNA and CDNs) and the formation of cGAMP. The cGAMP acts as a second messenger to activate STING-and TANK-binding kinase 1-mediated generation of type 1 IFNs and the activation of NF-B. The third section of the article describes the role of cGAS-STING signaling in the induction of autoinflammation and various autoimmune diseases. The subsequent fourth section describes both chemical compounds developed and the endogenous negative regulators of cGAS-STING signaling required for its regulation. Therapeutic targeting of cGAS-STING signaling could offer new ways to treat inflammatory and autoimmune diseases. K E Y W O R D S

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“…However, the molecular mechanisms underlying these immunostimulatory effects have not yet been elucidated as these nanoparticles have only recently been discovered. Macrophages are a type of phagocytotic immune cell which primarily exert immunostimulatory effects, such as inflammatory responses (6). The inflammatory response mediated by macrophages are induced by pattern recognition receptors, such as Toll-like receptors (TLRs) (7,8) and Dectin-1 (9,10).…”

Section: Introductionmentioning

confidence: 99%

Immunostimulatory effects of cell wall‑based nanoparticles in boiled Glycyrrhizae radix water extracts involves TLR4

et al. 2020

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A number of immunostimulant effects of herbal medicines have been reported; however, the underlying mechanisms of their immunostimulatory effects have not been elucidated in detail. Our previous study showed that sugar-based nanoparticles derived from cell walls acted as the immunostimulatory component of boiled Glycyrrhizae radix water extracts. Therefore, the aim of the present study was to clarify the molecular mechanisms by which these cell wall-based nanoparticles functioned as immunostimulants. Mouse macrophage RAW-blue cells were stimulated by these nanoparticles and several immunological effects were investigated. When phosphorylation of nuclear factor-κB (NF)-κB p65 subunit was increased, the expression of the inflammatory cytokines interleukin-6 and tumor necrosis factor-α were induced via NF-κB. On the other hand, Toll-like receptor 4 recognizes cell wall components of bacteria and fungi. In the present study, it was also shown that these cell wall-based nanoparticles serve an immunostimulatory role as ligands of Toll-like receptor 4 by RNA interference experiments. The results of the present study suggested that the signaling pathway of nanoparticles obtained from boiled Glycyrrhizae radix water extracts, at least partially involved TLR4 and downstream signaling from this receptor, resulting in the immunostimulatory effects of these nanoparticles in RAW-blue cells.

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Macrophage Extracellular Traps: A Scoping Review

Cited by 185 publications

References 60 publications

Neutrophil Extracellular Traps (NETs) in the Cerebrospinal Fluid Samples from Children and Adults with Central Nervous System Infections

Neutrophil Extracellular Traps (NETs) in the Cerebrospinal Fluid Samples from Children and Adults with Central Nervous System Infections

A STING to inflammation and autoimmunity

Immunostimulatory effects of cell wall‑based nanoparticles in boiled Glycyrrhizae radix water extracts involves TLR4

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