Biological Roles of Neutrophil-Derived Granule Proteins and Cytokines

Cassatella, Marco A.; Östberg, Nataliya K.; Tamassia, Nicola; Soehnlein, Oliver

doi:10.1016/j.it.2019.05.003

Cited by 179 publications

(185 citation statements)

References 138 publications

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“…During phagocytosis, neutrophils utilise a combination of surface-expressed opsonic receptors, intracellular signalling cascades, and cytoskeletal rearrangements to engulf and internalise microbes [14,15]. Neutrophils contain cytoplasmic granules, which store antimicrobial molecules and facilitate cross-talk with other immune cells [16]. These granules (summarised in Table 1) are subdivided into primary or azurophilic granules (containing, e.g., myeloperoxidase, CD63), secondary or specific granules (containing, e.g., lipocalin-2 and lactoferrin), and tertiary or gelatinase granules (containing, e.g., cathelicidins and neutrophil collagenase) [16].…”

Section: Neutrophils Deploy a Diverse Anti-microbial Arsenal Against mentioning

confidence: 99%

The Contribution of Neutrophils to the Pathogenesis of RSV Bronchiolitis

Sebina

Phipps

2020

Viruses

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Acute viral bronchiolitis causes significant mortality in the developing world, is the number one cause of infant hospitalisation in the developed world, and is associated with the later development of chronic lung diseases such as asthma. A vaccine against respiratory syncytial virus (RSV), the leading cause of viral bronchiolitis in infancy, remains elusive, and hence new therapeutic modalities are needed to limit disease severity. However, much remains unknown about the underlying pathogenic mechanisms. Neutrophilic inflammation is the predominant phenotype observed in infants with both mild and severe disease, however, a clear understanding of the beneficial and deleterious effects of neutrophils is lacking. In this review, we describe the multifaceted roles of neutrophils in host defence and antiviral immunity, consider their contribution to bronchiolitis pathogenesis, and discuss whether new approaches that target neutrophil effector functions will be suitable for treating severe RSV bronchiolitis.

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Section: Neutrophils Deploy a Diverse Anti-microbial Arsenal Against mentioning

confidence: 99%

The Contribution of Neutrophils to the Pathogenesis of RSV Bronchiolitis

Sebina

Phipps

2020

Viruses

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“…PMNs combat pathogens by undergoing degranulation events to rapidly release preformed stores of cytokines and there is a hierarchy in terms of time to PMN granule release, which contain both similar and dissimilar cytokines. 38,69,70 The actin cytoskeleton network controls neutrophil granule access to the plasma membrane and the exocytosis of granule contents. Disruption of the actin cytoskeleton following treatment with Latrunculin A decreases basal actin turnover and prevents elongation of actin filaments upon stimulation, which modifies release of a subset of granules.…”

Section: Control + Chxmentioning

confidence: 99%

Treponema denticola stimulates Oncostatin M cytokine release and de novo synthesis in neutrophils and macrophages

Jones

Vanyo

Ibraheem

et al. 2020

Journal of Leukocyte Biology

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Oncostatin M (OSM) is a pleiotropic cytokine elevated in a number of inflammatory conditions including periodontal disease. OSM is produced by a variety of immune cells and has diverse functionality such as regulation of metabolic processes, cell differentiation, and the inflammatory response to bacterial pathogens. The oral cavity is under constant immune surveillance including complementary neutrophil and macrophage populations, due to a persistent symbiotic bacterial presence. Periodontal disease is characterized by a dysbiotic bacterial community, with an abundance of Treponema denticola. Despite strong associations with severe periodontal disease, the source and mechanism of the release of OSM have not been defined in the oral cavity. We show that OSM protein is elevated in the gingival epithelium and immune cell infiltrate during periodontal disease. Furthermore, salivary and oral neutrophil OSM is elevated in correlation with the presence of T. denticola. In an air pouch infection model, T. denticola stimulated higher levels of OSM than the oral pathogen Porphorymonas gingivalis, despite differential recruitment of innate immune cells suggesting T. denticola has distinct properties to elevate OSM levels. OSM release and transcription were increased in isolated human blood, oral neutrophils, or macrophages exposed to T. denticola in vitro as measured by ELISA, qPCR, and microscopy. Using transcription, translation, and actin polymerization inhibition, we found that T. denticola stimulates both OSM release through degranulation and de novo synthesis in neutrophils and also OSM release and synthesis in macrophages. Differential induction of OSM by T. denticola may promote clinical periodontal disease.

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“…Neutrophils are equipped with a number of cytotoxic mechanisms designed to recognise and eliminate pathogens promptly, and hence play an early and vital role in host defence. A key component of this weaponry is the release of pre-formed membrane-bound granules, which are situated in the cytoplasm and packaged with multiple microbicidal proteins and proteases [2]. In order to affect pathogen killing, these granules can fuse with the pathogen-containing phagosome, releasing their toxic contents into the vacuole to destroy the ingested micro-organisms.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Hypoxia on Neutrophil Degranulation and Consequences for the Host

Lodge

Cowburn

et al. 2020

IJMS

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Neutrophils are key effector cells of innate immunity, rapidly recruited to defend the host against invading pathogens. Neutrophils may kill pathogens intracellularly, following phagocytosis, or extracellularly, by degranulation and the release of neutrophil extracellular traps; all of these microbicidal strategies require the deployment of cytotoxic proteins and proteases, packaged during neutrophil development within cytoplasmic granules. Neutrophils operate in infected and inflamed tissues, which can be profoundly hypoxic. Neutrophilic infiltration of hypoxic tissues characterises a myriad of acute and chronic infectious and inflammatory diseases, and as well as potentially protecting the host from pathogens, neutrophil granule products have been implicated in causing collateral tissue damage in these scenarios. This review discusses the evidence for the enhanced secretion of destructive neutrophil granule contents observed in hypoxic environments and the potential mechanisms for this heightened granule exocytosis, highlighting implications for the host. Understanding the dichotomy of the beneficial and detrimental consequences of neutrophil degranulation in hypoxic environments is crucial to inform potential neutrophil-directed therapeutics in order to limit persistent, excessive, or inappropriate inflammation.

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Biological Roles of Neutrophil-Derived Granule Proteins and Cytokines

Cited by 179 publications

References 138 publications

The Contribution of Neutrophils to the Pathogenesis of RSV Bronchiolitis

The Contribution of Neutrophils to the Pathogenesis of RSV Bronchiolitis

Treponema denticola stimulates Oncostatin M cytokine release and de novo synthesis in neutrophils and macrophages

The Impact of Hypoxia on Neutrophil Degranulation and Consequences for the Host

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