NETosis and Neutrophil Extracellular Traps in COVID-19: Immunothrombosis and Beyond DOI Creative Commons
Yuanfeng Zhu, Xiaoli Chen, Xin Liu

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: March 2, 2022

Infection with SARS-CoV-2, the causative agent of Coronavirus disease 2019 (COVID-19) pandemic, causes respiratory problems and multifaceted organ dysfunction. A crucial mechanism COVID-19 immunopathy is recruitment activation neutrophils at infection site, which also predicts severity poor outcomes. The release neutrophil extracellular traps (NETs), occurring during a regulated form cell death known as NETosis, key effector function that mediates harmful effects caused by neutrophils. Abundant NETosis NET generation have been observed in many patients, leading to unfavorable coagulopathy immunothrombosis. Moreover, excessive are now more widely recognized mediators additional pathophysiological abnormalities following SARS-CoV-2 infection. In this minireview, we introduce subtypes NET-producing (e.g., low-density granulocytes) explain biological importance NETs protein cargos COVID-19. addition, discuss mechanisms upregulating viral processes entry replication) well host pro-NET proinflammatory mediator release, platelet activation, autoantibody production). Furthermore, provide an update main findings immunothrombosis other COVID-19-related disorders, such aberrant immunity, neurological post syndromes including lung fibrosis, disorder, tumor progression, deteriorated chronic illness. Finally, address potential prospective treatment strategies target dysregulated formation via inhibition promotion degradation, respectively.

Language: Английский

Regulatory T cell control of systemic immunity and immunotherapy response in liver metastasis DOI
James Lee, Sadaf Mehdizadeh, Jennifer A. Smith

et al.

Science Immunology, Journal Year: 2020, Volume and Issue: 5(52)

Published: Oct. 2, 2020

Liver metastasis suppresses systemic tumor-specific immunity and contributes to the resistance checkpoint immunotherapy.

Language: Английский

Citations

223
Neutrophil phenotypes and functions in cancer: A consensus statement DOI Creative Commons

Daniela F. Quail,

Borko Amulic, Monowar Aziz

et al.

The Journal of Experimental Medicine, Journal Year: 2022, Volume and Issue: 219(6)

Published: May 6, 2022

Neutrophils are the first responders to infection and inflammation thus a critical component of innate immune defense. Understanding behavior neutrophils as they act within various inflammatory contexts has provided insights into their role in sterile infectious diseases; however, field cancer is comparatively young. Here, we summarize key concepts current knowledge gaps related diverse roles throughout progression. We discuss sources neutrophil heterogeneity provide recommendations on nomenclature for states that distinct maturation activation. address discrepancies literature highlight need technical standards ought be considered between laboratories. Finally, review emerging questions biology immunity cancer. Overall, emphasize more population than previously appreciated may present novel unexplored opportunities treat

Language: Английский

Citations

218
A neutrophil response linked to tumor control in immunotherapy DOI Creative Commons
Jeremy Gungabeesoon, Nicolas A. Gort-Freitas, Máté Kiss

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(7), P. 1448 - 1464.e20

Published: March 1, 2023

Language: Английский

Citations

212
Neutrophil extracellular traps: from physiology to pathology DOI
Andrés Hidalgo, Peter Libby, Oliver Soehnlein

et al.

Cardiovascular Research, Journal Year: 2021, Volume and Issue: 118(13), P. 2737 - 2753

Published: Oct. 12, 2021

Abstract At the frontline of host defence response, neutrophil antimicrobial functions have adapted to combat infections and injuries different origins magnitude. The release web-like DNA structures named extracellular traps (NETs) constitutes an important mechanism by which neutrophils prevent pathogen dissemination or deal with microorganisms a bigger size. same time, nuclear granule proteins microbicidal activity bind these promoting elimination entrapped pathogens. However, toxic properties may produce unwanted effects in host, when uncontrollably NETs upon persistent inflammation. As consequence, NET accumulation can vessel occlusion, tissue damage, prolonged inflammation associated progression exacerbation multiple pathologic conditions. This review outlines recent advances understanding mechanisms sterile disease. We also discuss physiological regulation importance heterogeneity formation composition.

Language: Английский

Citations

204
Neutrophil extracellular traps mediate m6A modification and regulates sepsis-associated acute lung injury by activating ferroptosis in alveolar epithelial cells DOI Creative Commons
Hao Zhang, Jinlong Liu, Yilu Zhou

et al.

International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 18(8), P. 3337 - 3357

Published: Jan. 1, 2022

Neutrophil extracellular traps (NETs) production is a major strategy employed by polymorphonuclear neutrophils (PMNs) to fight against microbes. NETs have been implicated in the pathogenesis of various lung injuries, although few studies explored sepsis-associated acute injury (SI-ALI). Here, we demonstrate contribution pathology ALI inducing ferroptosis alveolar epithelial cells. Using both vitro and vivo studies, our findings show enhanced accumulation patients mice, as well closely related upregulation ferroptosis, induction which depends on METTL3-induced m6A modification GPX4. CLP-induced mouse model established with METTL3-/- versus WT addition METTL3 knockout overexpression vitro, elucidated confirmed critical role NETs-induced ALI. These support for subsequent

Language: Английский

Citations

193
Activating a collaborative innate-adaptive immune response to control metastasis DOI Creative Commons
Lijuan Sun,

Tim Kees,

Ana S. Almeida

et al.

Cancer Cell, Journal Year: 2021, Volume and Issue: 39(10), P. 1361 - 1374.e9

Published: Sept. 2, 2021

Language: Английский

Citations

190
IL8, Neutrophils, and NETs in a Collusion against Cancer Immunity and Immunotherapy DOI Open Access
Álvaro Teijeira, Saray Garasa, María C. Ochoa

et al.

Clinical Cancer Research, Journal Year: 2020, Volume and Issue: 27(9), P. 2383 - 2393

Published: Dec. 29, 2020

Abstract One of the most important mechanisms by which cancer fosters its own development is generation an immune microenvironment that inhibits or impairs antitumor responses. A permissive present in a large proportion patients with who do not respond to immunotherapy approaches intended trigger preexisting responses, for instance, checkpoint blockade. High circulating levels IL8 quite accurately predict those will benefit from checkpoint-based immunotherapy. has been reported favor progression and metastases via different mechanisms, including proangiogenesis maintenance stem cells, but ability attract functionally modulate neutrophils macrophages arguably one factors. does only recruit tumor lesions, also triggers extrusion neutrophil extracellular traps (NET). The relevance underlying contribution both NETs are starting be uncovered include direct effects on cells changes microenvironment, such as facilitating metastasis, awakening micrometastases dormancy, escape cytotoxic cells. Blockade receptors (CXCR1 CXCR2) being pursued drug development, clinical trials alone combination anti-PD-L1 inhibitors already ongoing.

Language: Английский

Citations

183
Neutrophil Extracellular Traps and Their Implications in Cardiovascular and Inflammatory Disease DOI Open Access
Johannes Klopf, Christine Brostjan, Wolf Eilenberg

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(2), P. 559 - 559

Published: Jan. 8, 2021

Neutrophils are primary effector cells of innate immunity and fight infection by phagocytosis degranulation. Activated neutrophils also release neutrophil extracellular traps (NETs) in response to a variety stimuli. These NETs net-like complexes composed cell-free DNA, histones granule proteins. Besides the evolutionarily conserved mechanism capture eliminate pathogens, associated with pathophysiological processes various diseases. Here, we elucidate mechanisms NET formation their different implications disease. We focused on autoinflammatory cardiovascular disorders as leading cause death. Neutrophil not only present diseases but play an essential role atherosclerotic plaque formation, arterial venous thrombosis, well development progression abdominal aortic aneurysms. Furthermore, NETosis can be considered source autoantigens maintains inflammatory milieu promoting autoimmune Indeed, there is further need for research into balance between induction, inhibition, degradation order pharmacologically target compounds without impairing patient's immune defense. This review may interest both basic scientists clinicians stimulate translational innovative clinical approaches.

Language: Английский

Citations

171
T cell immunotherapies engage neutrophils to eliminate tumor antigen escape variants DOI Creative Commons
Daniel Hirschhorn, Sadna Budhu, Lukas Kraehenbuehl

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(7), P. 1432 - 1447.e17

Published: March 1, 2023

Language: Английский

Citations

160
Neutrophil Extracellular Traps (NETs) in Cancer Invasion, Evasion and Metastasis DOI Open Access
Urszula Demkow

Cancers, Journal Year: 2021, Volume and Issue: 13(17), P. 4495 - 4495

Published: Sept. 6, 2021

The present review highlights the complex interactions between cancer and neutrophil extracellular traps (NETs). Neutrophils constitute first line of defense against foreign invaders using major effector mechanisms: phagocytosis, degranulation, NETs formation. are composed from decondensed nuclear or mitochondrial DNA decorated with proteases various inflammatory mediators. Although play a crucial role in systemic infections, they also participate non-infectious conditions, such as inflammation, autoimmune disorders, cancer. Cancer cells recruit neutrophils (tumor-associated neutrophils, TANs), releasing to tumor microenvironment. were found samples human animal tumors, pancreatic, breast, liver, gastric cancers around metastatic tumors. development increasingly includes immunoediting immune system cells. According accumulated evidence, awake dormant cells, causing relapse, well its unconstrained growth spread. key regulatory microenvironment, distant metastases through secretion proteases, i.e., matrix metalloproteinases proinflammatory cytokines. NETs, furthermore, directly exacerbate aggressiveness by enhancing migration invasion capacity. collected evidence states that induction high-mobility group box 1, induce epithelial mesenchymal transition and, thereby, potentiate their invasiveness. NET proteinases can degrade matrix, promoting cell extravasation. Moreover, entrap circulating way, facilitate metastasis. trigger proliferation activating signals. This focused on pro-tumorigenic action spite potential exhibit an antitumor effect. components, myeloperoxidase histones, have been shown kill A better understanding crosstalk help devise novel approaches therapeutic interventions block evasion mechanisms prevent sought provide most recent knowledge cancer, bring more profound ideas for future scientists exploring this field.

Language: Английский

Citations

150