The Neutrophil

Burn, Garth L.; Foti, Alessandro; Marsman, Gerben; Patel, Dhiren F.; Zychlinsky, Arturo

doi:10.1016/j.immuni.2021.06.006

Cited by 348 publications

(277 citation statements)

References 184 publications

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“…Usually, neutrophils are the first immune cell to reach inflamed tissue (Liew and Kubes, 2019). Neutrophils are polymorphonuclear segmented cells with antimicrobial properties (Burn et al, 2021). However, these cells present many other immune functions and participate in the stimulation of adaptive immune responses (Minns et al, 2019), in the resolution of inflammation (Jones et al, 2016) and healing (Phillipson and Kubes, 2019), and have anti or pro-tumor activity (Mishalian et al, 2017;Ocana et al, 2017;Burn et al, 2021).…”

Section: Neutrophils: Modulation By Ouabainmentioning

confidence: 99%

Neuroinflammation and Neutrophils: Modulation by Ouabain

et al. 2022

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Cardiotonic steroids are natural compounds that present many physiological and pharmacological functions. They bind Na+/K+-ATPase (NKA) modifying cellular ion concentration and trigger cell signaling mechanisms without altering ion balance. These steroids are known to modulate some immune responses, including cytokine production, neutrophil migration, and inflammation (peripherally and in the nervous system). Inflammation can occur in response to homeostasis perturbations and is related to the development of many diseases, including immune-mediated diseases and neurodegenerative disorders. Considering the neutrophils role in the general neuroinflammatory response and that these cells can be modulated by cardiac steroids, this work aims to review the possible regulation of neutrophilic neuroinflammation by the cardiac steroid ouabain.

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Section: Neutrophils: Modulation By Ouabainmentioning

confidence: 99%

Neuroinflammation and Neutrophils: Modulation by Ouabain

et al. 2022

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“…Single-cell RNA sequencing (scRNA-seq) has revolutionized our understanding of immune cell development, maturation, and functional plasticity [ 68 ]. However, neutrophil biologists have historically placed little emphasis on transcriptional regulation of neutrophil functions, since mature circulating neutrophils display relatively low transcriptional activity, and their cardinal effector functions (e.g., phagocytosis, oxidative bursts, NETs, proteolysis) are largely regulated at post-transcriptional and post-translational levels [ 1 , 2 ]. In addition, neutrophils are technically challenging to study in vast scRNA-seq datasets (especially those derived from in vivo tissues) due to their relatively low transcript counts in sequencing datasets that render these cells susceptible to filtering algorithms based on read count thresholds.…”

Section: A Renaissance In Neutrophil Biology—high-dimensional Multi-omics Analysis Of Neutrophilsmentioning

confidence: 99%

“…Neutrophils are powerful immune effector cells that maintain homeostasis in health, fight infections, and participate (for better or worse) across a spectrum of diseases including an expanding role in immuno-oncology. Our understanding of neutrophil biology in health and disease has grown exponentially in recent years, as has our appreciation of the complex bi-directional interplay between neutrophils and other innate and adaptive immune cells, stromal cells, and tissue niches [ 1 , 2 ]. As such, contemporary neutrophil biology is moving towards a systems biology approach to understanding the cellular functions and biological contributions of these critical immune cells in vivo [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

A Multi-Modal Toolkit for Studying Neutrophils in Cancer and Beyond

Changirwa

Schlechte

McDonald

2021

Cancers

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As key effector cells of the innate immune response, neutrophils are rapidly deployed to sites of inflammation where they deliver a payload of potent effector mechanisms that are essential for host defense against pathogens as well as tissue homeostasis. In addition, neutrophils are central contributors to the pathogenesis of a vast spectrum of inflammatory, degenerative, and neoplastic diseases. As our understanding of neutrophils in health and disease continually expands, so too does our appreciation of their complex and dynamic nature in vivo; from development, maturation, and trafficking to cellular heterogeneity and functional plasticity. Therefore, contemporary neutrophil research relies on multiple complementary methodologies to perform integrated analysis of neutrophil phenotypic heterogeneity, organ- and stimulus-specific trafficking mechanisms, as well as tailored effector functions in vivo. This review discusses established and emerging technologies used to study neutrophils, with a focus on in vivo imaging in animal models, as well as next-generation ex vivo model systems to study mechanisms of neutrophil function. Furthermore, we discuss how high-dimensional single-cell analysis technologies are driving a renaissance in neutrophil biology by redefining our understanding of neutrophil development, heterogeneity, and functional plasticity. Finally, we discuss innovative applications and emerging opportunities to integrate these high-dimensional, multi-modal techniques to deepen our understanding of neutrophils in cancer research and beyond.

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“…Neutrophils are the most abundant cells of the innate immune system and play a key role in antimicrobial and antifungal defenses ( 1 ). At the site of infection, pathogens are detected via pattern recognition receptors (PRRs) whose ligation leads to the activation of a complex network of signaling cascades that together orchestrate the neutrophil’s ability to kill microbes via the generation of reactive oxygen species (ROS), degranulation of effector molecules, and the release of neutrophil extracellular traps (NETs) ( 2 , 3 ). Moreover, these signaling pathways stimulate the production and release of chemokines and cytokines by neutrophils that act both locally, recruiting other immune cells to the site, and systemically, to regulate the wider anti-microbial immune response ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

Immunosuppression Affects Neutrophil Functions: Does Calcineurin-NFAT Signaling Matter?

et al. 2021

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Neutrophils are innate immune cells with important roles in antimicrobial defense. However, impaired or dysregulated neutrophil function can result in host tissue damage, loss of homeostasis, hyperinflammation or pathological immunosuppression. A central link between neutrophil activation and immune outcomes is emerging to be the calcineurin-nuclear factor of activated T cells (NFAT) signaling pathway, which is activated by neutrophil detection of a microbial threat via pattern recognition receptors and results in inflammatory cytokine production. This potent pro-inflammatory pathway is also the target of several immunosuppressive drugs used for the treatment of autoimmune disorders, during solid organ and hematopoietic cell transplantations, and as a part of anti-cancer therapy: but what effects these drugs have on neutrophil function, and their broader consequences for immune homeostasis and microbial defense are not yet known. Here, we bring together the emerging literature describing pathology- and drug- induced neutrophil impairment, with particular focus on their effects on calcineurin-NFAT signaling in the innate immune compartment.

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The Neutrophil

Cited by 348 publications

References 184 publications

Neuroinflammation and Neutrophils: Modulation by Ouabain

Neuroinflammation and Neutrophils: Modulation by Ouabain

A Multi-Modal Toolkit for Studying Neutrophils in Cancer and Beyond

Immunosuppression Affects Neutrophil Functions: Does Calcineurin-NFAT Signaling Matter?

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