Nano- and Microparticles and Their Role in Inflammation and Immune Response: Focus on Neutrophil Extracellular Traps

Severe cases of coronavirus disease 2019 (COVID-19), caused by infection with SARS-Cov-2, are characterized by a hyperinflammatory immune response that leads to numerous complications. Production of proinflammatory neutrophil extracellular traps (NETs) has been suggested to be a key factor in inducing a hyperinflammatory signaling cascade, allegedly causing both pulmonary tissue damage and peripheral inflammation. Accordingly, therapeutic blockage of neutrophil activation and NETosis, the cell death pathway accompanying NET formation, could limit respiratory damage and death from severe COVID-19. Here, we demonstrate that synthetic glycopolymers that activate the neutrophil checkpoint receptor Siglec-9 suppress NETosis induced by agonists of viral toll-like receptors (TLRs) and plasma from patients with severe COVID-19. Thus, Siglec-9 agonism is a promising therapeutic strategy to curb neutrophilic hyperinflammation in COVID-19.<br>

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Neutrophil Extracellular Traps (NETs) and Damage-Associated Molecular Patterns (DAMPs): Two Potential Targets for COVID-19 Treatment

Mediators of Inflammation ◽

10.1155/2020/7527953 ◽

2020 ◽

Vol 2020 ◽

pp. 1-25 ◽

Cited By ~ 11

Author(s):

Sebastiano Cicco ◽

Gerolamo Cicco ◽

Vito Racanelli ◽

Angelo Vacca

Keyword(s):

Immune Response ◽

Innate Immunity ◽

Targeted Therapy ◽

High Mobility ◽

Neutrophil Extracellular Traps ◽

Lung Cells ◽

Extracellular Traps ◽

Molecular Patterns ◽

Damage Associated Molecular Patterns ◽

Excessive Inflammatory Response

COVID-19 is a pandemic disease caused by the new coronavirus SARS-CoV-2 that mostly affects the respiratory system. The consequent inflammation is not able to clear viruses. The persistent excessive inflammatory response can build up a clinical picture that is very difficult to manage and potentially fatal. Modulating the immune response plays a key role in fighting the disease. One of the main defence systems is the activation of neutrophils that release neutrophil extracellular traps (NETs) under the stimulus of autophagy. Various molecules can induce NETosis and autophagy; some potent activators are damage-associated molecular patterns (DAMPs) and, in particular, the high-mobility group box 1 (HMGB1). This molecule is released by damaged lung cells and can induce a robust innate immunity response. The increase in HMGB1 and NETosis could lead to sustained inflammation due to SARS-CoV-2 infection. Therefore, blocking these molecules might be useful in COVID-19 treatment and should be further studied in the context of targeted therapy.

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Proteomic Characterization of Middle Ear Fluid Confirms Neutrophil Extracellular Traps as a Predominant Innate Immune Response in Chronic Otitis Media

PLoS ONE ◽

10.1371/journal.pone.0152865 ◽

2016 ◽

Vol 11 (4) ◽

pp. e0152865 ◽

Cited By ~ 19

Author(s):

Stephanie Val ◽

Marian Poley ◽

Kristy Brown ◽

Rachel Choi ◽

Stephanie Jeong ◽

...

Keyword(s):

Immune Response ◽

Otitis Media ◽

Innate Immune Response ◽

Middle Ear ◽

Chronic Otitis Media ◽

Neutrophil Extracellular Traps ◽

Innate Immune ◽

Extracellular Traps ◽

Middle Ear Fluid

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The Dual Role of Myeloperoxidase in Immune Response

International Journal of Molecular Sciences ◽

10.3390/ijms21218057 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8057 ◽

Cited By ~ 1

Author(s):

Jürgen Arnhold

Keyword(s):

Immune Response ◽

Innate Immune System ◽

Neutrophil Extracellular Traps ◽

Innate Immune ◽

Major Constituent ◽

Extracellular Traps ◽

Atherosclerotic Lesions ◽

Disease Specific ◽

Frustrated Phagocytosis

The heme protein myeloperoxidase (MPO) is a major constituent of neutrophils. As a key mediator of the innate immune system, neutrophils are rapidly recruited to inflammatory sites, where they recognize, phagocytose, and inactivate foreign microorganisms. In the newly formed phagosomes, MPO is involved in the creation and maintenance of an alkaline milieu, which is optimal in combatting microbes. Myeloperoxidase is also a key component in neutrophil extracellular traps. These helpful properties are contrasted by the release of MPO and other neutrophil constituents from necrotic cells or as a result of frustrated phagocytosis. Although MPO is inactivated by the plasma protein ceruloplasmin, it can interact with negatively charged components of serum and the extracellular matrix. In cardiovascular diseases and many other disease scenarios, active MPO and MPO-modified targets are present in atherosclerotic lesions and other disease-specific locations. This implies an involvement of neutrophils, MPO, and other neutrophil products in pathogenesis mechanisms. This review critically reflects on the beneficial and harmful functions of MPO against the background of immune response.

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ROLE OF NEUTROPHIL EXTRACELLULAR TRAPS IN ESPECIALLY DANGEROUS BACTERIAL INFECTIONS

Journal of microbiology epidemiology immunobiology ◽

10.36233/0372-9311-2016-4-95-104 ◽

2016 ◽

pp. 95-104

Author(s):

A. L. Kravtsov

Keyword(s):

Experimental Data ◽

Immune Response ◽

Bacterial Infections ◽

Neutrophil Extracellular Traps ◽

Bactericidal Effect ◽

Pathogenic Microorganisms ◽

Extracellular Traps ◽

Contemporary View ◽

Causative Agents

Novel data on neutrophil extracellular traps (NET), carrying out capture and killing of pathogenic microorganisms with higher effectiveness than during phagocytosis, are presented. A contemporary view on how neutrophils choose intracellular (phagocytosis) or extracellular (NETosis) mechanism of bactericidity during interaction with pathogenic microorganisms is given. Experimental data on the presence in causative agents of plague, cholera and melioidosis of mechanisms of protection from bactericidal effect of NET, as well as NET’S role in regulation of immune response and sepsis development are analyzed.

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SARS-CoV2 may evade innate immune response, causing uncontrolled neutrophil extracellular traps formation and multi-organ failure

Clinical Science ◽

10.1042/cs20200531 ◽

2020 ◽

Vol 134 (12) ◽

pp. 1295-1300 ◽

Cited By ~ 6

Author(s):

Alain R. Thierry ◽

Benoit Roch

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Rapid Evolution ◽

Neutrophil Extracellular Traps ◽

Innate Immune ◽

Biological Features ◽

Extracellular Traps ◽

Clinical Conditions ◽

By Products ◽

New Strategies

Abstract We demonstrate that the general clinical conditions, risk factors and numerous pathological and biological features of COVID-19 are analogous with various disorders caused by the uncontrolled formation of neutrophil extracellular traps and their by-products. Given the rapid evolution of this disease’s symptoms and its lethality, we hypothesize that SARS-CoV2 evades innate immune response causing COVID-19 progresses under just such an amplifier loop, leading to a massive, uncontrolled inflammation process. This work allows us to propose new strategies for treating the pandemic.

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Rapid Generation of Coronaviral Immunity Using Recombinant Peptide Modified Nanodiamonds

Pathogens ◽

10.3390/pathogens10070861 ◽

2021 ◽

Vol 10 (7) ◽

pp. 861

Author(s):

Rostyslav Bilyy ◽

Quentin Pagneux ◽

Nathan François ◽

Galyna Bila ◽

Roman Grytsko ◽

...

Keyword(s):

Immune Response ◽

Neutrophil Extracellular Traps ◽

Fusion Inhibitor ◽

Recombinant Peptide ◽

Vaccine Candidates ◽

Extracellular Traps ◽

Vaccine Initiation ◽

Rapid Generation ◽

Living Organisms ◽

High Level

Vaccination remains one of the most effective tools to prevent infectious diseases. To ensure that the best possible antigenic components are chosen to stimulate a cognitive immune response, boosting antigen presentation using adjuvants is common practice. Nanodiamond-based adjuvants are proposed here as a rapid and versatile platform for antigen conjugation, utilizing peptides common to different pathogenic strains and making this strategy a good candidate for a “ready-to-use” vaccine. Initiation of an inflammatory reaction with a resulting immune response is based on the ability of living organisms to entrap nanostructures such as nanodiamonds with neutrophil extracellular traps (NETs) formation. In this work, coronavirus peptide homological for MERS-CoV, fusion inhibitor, was conjugated to nanodiamonds and used to induce neutrophilic-driven self-limiting inflammation. The resulting adjuvant was safe and did not induce any tissue damage at the site of injection. Mice immunization resulted in IgG titers of ¼,000 within 28 days. Immunization of rabbits resulted in the formation of a high level of antibodies persistently present for up to 120 days after the first immunization (animal lifespan ~3 years). The peptide used for immunization proved to be reactive with sera of convalescent COVID patients, demonstrating the possibility of developing pancoronaviral vaccine candidates.

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The intriguing host innate immune response: novel anti-parasitic defence by neutrophil extracellular traps

Parasitology ◽

10.1017/s0031182014000316 ◽

2014 ◽

Vol 141 (11) ◽

pp. 1489-1498 ◽

Cited By ~ 47

Author(s):

CARLOS HERMOSILLA ◽

TAMARA MUÑOZ CARO ◽

LILIANA M. R. SILVA ◽

ANTONIO RUIZ ◽

ANJA TAUBERT

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Nuclear Dna ◽

Neutrophil Extracellular Traps ◽

Innate Immune ◽

Polymorphonuclear Neutrophils ◽

Metazoan Parasites ◽

Related Data ◽

Extracellular Traps ◽

Host Innate Immune Response

SUMMARYThe capacity of polymorphonuclear neutrophils (PMN) and other leucocytes of the innate immune system to expel their DNA in a controlled process into the extracellular environment to trap and kill pathogenic microorganisms led to a paradigm shift in our comprehension of host leucocyte-pathogen interactions. Formation of neutrophil extracellular traps (NETs) has recently been recognized as a novel effector mechanism of the host innate immune response against microbial infections. Meanwhile evidence has arisen that NET formation is a widely spread mechanism in vertebrates and invertebrates and extends not only to the entrapment of microbes, fungi and viruses but also to the capture of protozoan and metazoan parasites. PMN produce NETs after stimulation with mitogens, cytokines or pathogens in a controlled process which depends on reactive oxygen species (ROS) and the induction of the Raf-MEK-ERK-mediated signalling pathway cascade. NETs consist of nuclear DNA as a backbone decorated with histones, antimicrobial peptides, and PMN-specific granular enzymes thereby providing an extracellular matrix capable of entrapping and killing invasive pathogens. This review is intended to summarize parasite-related data on NETs. Special attention will be given to NET-associated mechanisms by which parasites, in particular apicomplexa, might be hampered in their ability to reproduce within the host cell and complete the life cycle.

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