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Neutrophil Functions: From Immunity to Disease

A special issue of Journal of Clinical Medicine (ISSN 2077-0383).

Deadline for manuscript submissions: closed (31 July 2016)

Special Issue Editors


E-Mail Website1 Website2
Guest Editor
1. Aix Marseille Université, INSERM 1263, INRAE, C2VN, 13885 Marseille, France
2. Department of Oral and Maxillofacial Surgery, Laveran Military and Academic Hospital, 13384 Marseille, France
Interests: platelets; thrombosis; neutrophils; cancer; inflammation; intravital microscopy

E-Mail Website
Guest Editor
Vascular Research Center of Marseille (VRCM), Aix Marseille University, Faculty of Pharmacy, 27 bd Jean Moulin, 13385 Marseille, France
Interests: platelets; thrombosis; neutrophils; cancer; inflammation; intravital microscopy

Special Issue Information

Dear Colleagues,

Neutrophils have been described as key players in innate immunity for decades. Until recently, neutrophils functions were mainly studied as an essential partner of the immune response in inflammation and involved in different diseases, such as allergy, atherosclerosis, sepsis, asthma, and arthritis. The participation of Neutrophil Extracellular Traps (NETs) induced by the priming and activation of neutrophils to trap bacteria has also been described to constitute an early step, essential to limit the spread of a pathogen.

Thanks to the technological evolutions of intravital microscopy and the development of new tools allowing in vivo imaging, the involvement of neutrophil and NETS have recently been extended to other diseases. Neutrophils have been described to play a key role in cancer, metastasis development via the accumulation of TIN (for tumor infiltrated neutrophils), and immunothrombosis through the activation of the blood coagulation cascade. The implication of NETs in deep vein thrombosis (DVT), pulmonary embolism, cancer, deep vein thrombosis, and the evolution of the Alzheimer disease are also actually intensively studied. This Special Issue will resume state-of-the-art studies on the new roles of neutrophils and NETS in healthy and pathological situations.

Prof. Christophe Dubois
Dr. Laurence Panicot-Dubois
Guest Editors

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Keywords

  • neutrophils
  • neutrophils extra cellular traps (NETs)
  • inflammation
  • immunothrombosis
  • thrombosis
  • platelets
  • cancer
  • real time in vivo imaging.

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Published Papers (3 papers)

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Review

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Review
Effector Mechanisms of Neutrophils within the Innate Immune System in Response to Mycobacterium tuberculosis Infection
by Eric Warren, Garrett Teskey and Vishwanath Venketaraman
J. Clin. Med. 2017, 6(2), 15; https://doi.org/10.3390/jcm6020015 - 7 Feb 2017
Cited by 40 | Viewed by 12692
Abstract
Neutrophils have a significant yet controversial role in the innate immune response to Mycobacterium tuberculosis (M. tb) infection, which is not yet fully understood. In addition to neutrophils’ well-known effector mechanisms, they may also help control infection of M. tb through [...] Read more.
Neutrophils have a significant yet controversial role in the innate immune response to Mycobacterium tuberculosis (M. tb) infection, which is not yet fully understood. In addition to neutrophils’ well-known effector mechanisms, they may also help control infection of M. tb through the formation of neutrophil extracellular traps (NETs), which are thought to further promote the killing of M. tb by resident alveolar macrophages. Cytokines such as IFN-γ have now been shown to serve an immunomodulatory role in neutrophil functioning in conjunction to its pro-inflammatory function. Additionally, the unique transcriptional changes of neutrophils may be used to differentiate between infection with M. tb and other bacterial and chronic rheumatological diseases such as Systemic Lupus Erythematosus. Adversely, during the innate immune response to M. tb, inappropriate phagocytosis of spent neutrophils can result in nonspecific damage to host cells due to necrotic lysis. Furthermore, some individuals have been shown to be more genetically susceptible to tuberculosis (TB) due to a “Trojan Horse” phenomenon whereby neutrophils block the ability of resident macrophages to kill M. tb. Despite these aforementioned negative consequences, through the scope of this review we will provide evidence to support the idea that neutrophils, while sometimes damaging, can also be an important component in warding off M. tb infection. This is exemplified in immunocompromised individuals, such as those with human immunodeficiency virus (HIV) infection or Type 2 diabetes mellitus. These individuals are at an increased risk of developing tuberculosis (TB) due to a diminished innate immune response associated with decreased levels of glutathione. Consequently, there has been a worldwide effort to limit and contain M. tb infection through the use of antibiotics and vaccinations. However, due to several significant limitations, the current bacille Calmette-Guerin vaccine (BCG, vaccine against TB) does not meet the criteria for universal utilization for all ages and populations across the globe. New research involving neutrophils has yielded a new vaccine called M. smegmatis-Ag85C-MPT51-HspX (mc2-CMX) that has been shown to elicit a humoral and cellular response against M. tb in mice that is superior to the BCG vaccine. Full article
(This article belongs to the Special Issue Neutrophil Functions: From Immunity to Disease)
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778 KiB  
Review
The Dual Role of Neutrophils in Inflammatory Bowel Diseases
by Odile Wéra, Patrizio Lancellotti and Cécile Oury
J. Clin. Med. 2016, 5(12), 118; https://doi.org/10.3390/jcm5120118 - 17 Dec 2016
Cited by 210 | Viewed by 15526
Abstract
Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are characterised by aberrant immunological responses leading to chronic inflammation without tissue regeneration. These two diseases are considered distinct entities, and there is some evidence that neutrophil behaviour, above all other aspects of [...] Read more.
Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are characterised by aberrant immunological responses leading to chronic inflammation without tissue regeneration. These two diseases are considered distinct entities, and there is some evidence that neutrophil behaviour, above all other aspects of immunity, clearly separate them. Neutrophils are the first immune cells recruited to the site of inflammation, and their action is crucial to limit invasion by microorganisms. Furthermore, they play an essential role in proper resolution of inflammation. When these processes are not tightly regulated, they can trigger positive feedback amplification loops that promote neutrophil activation, leading to significant tissue damage and evolution toward chronic disease. Defective chemotaxis, as observed in Crohn’s disease, can also contribute to the disease through impaired microbe elimination. In addition, through NET production, neutrophils may be involved in thrombo-embolic events frequently observed in IBD patients. While the role of neutrophils has been studied in different animal models of IBD for many years, their contribution to the pathogenesis of IBD remains poorly understood, and no molecules targeting neutrophils are used and validated for the treatment of these pathologies. Therefore, it is crucial to improve our understanding of their mode of action in these particular conditions in order to provide new therapeutic avenues for IBD. Full article
(This article belongs to the Special Issue Neutrophil Functions: From Immunity to Disease)
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1234 KiB  
Review
Repurposing Treatments to Enhance Innate Immunity. Can Statins Improve Neutrophil Functions and Clinical Outcomes in COPD?
by Georgia M. Walton, James A. Stockley, Diane Griffiths, Charandeep S. Sadhra, Thomas Purvis and Elizabeth Sapey
J. Clin. Med. 2016, 5(10), 89; https://doi.org/10.3390/jcm5100089 - 11 Oct 2016
Cited by 31 | Viewed by 7003
Abstract
Drug classes used in the treatment of Chronic Obstructive Pulmonary Disease (COPD) have not changed for many years, and none to date have shown disease-modifying activity. Statins are used to help reduce cardiovascular risk, which is high in many patients with COPD. Their [...] Read more.
Drug classes used in the treatment of Chronic Obstructive Pulmonary Disease (COPD) have not changed for many years, and none to date have shown disease-modifying activity. Statins are used to help reduce cardiovascular risk, which is high in many patients with COPD. Their use has been associated with improvements in some respiratory manifestations of disease and reduction in all-cause mortality, with greatest reductions seen in patients with the highest inflammatory burden. The mechanism for these effects is poorly understood. Neutrophils are key effector cells in COPD, and correlate with disease severity and inflammation. Recent in vitro studies have shown neutrophil functions are dysregulated in COPD and this is thought to contribute both to the destruction of lung parenchyma and to the poor responses seen in infective exacerbations. In this article, we will discuss the potential utility of statins in COPD, with a particular emphasis on their immune-modulatory effects as well as presenting new data regarding the effects of statins on neutrophil function in vitro. Full article
(This article belongs to the Special Issue Neutrophil Functions: From Immunity to Disease)
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