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

2020 ◽  
Vol 134 (12) ◽  
pp. 1295-1300 ◽  
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.

scholarly journals Neutrophil Extracellular Traps and By-Products Play a Key Role in COVID-19: Pathogenesis, Risk Factors, and Therapy

2020 ◽  
Vol 9 (9) ◽  
pp. 2942 ◽  
Author(s):  
Alain R. Thierry ◽  
Benoit Roch
Keyword(s):  
Risk Factors ◽  
Rapid Evolution ◽  
Neutrophil Extracellular Traps ◽  
Biological Features ◽  
Extracellular Traps ◽  
Formation Function ◽  
Dna Release ◽  
Amplification Loop ◽  
Clinical Conditions ◽  
By Products

Understanding of the pathogenesis of the coronavirus disease-2019 (COVID-19) remains incomplete, particularly in respect to the multi-organ dysfunction it may cause. We were the first to report the analogous biological and physiological features of COVID-19 pathogenesis and the harmful amplification loop between inflammation and tissue damage induced by the dysregulation of neutrophil extracellular traps (NETs) formation. Given the rapid evolution of this disease, the nature of its symptoms, and its potential lethality, we hypothesize that COVID-19 progresses under just such an amplifier loop, leading to a massive, uncontrolled inflammation process. Here, we describe in-depth the correlations of COVID-19 symptoms and biological features with those where uncontrolled NET formation is implicated in various sterile or infectious diseases. General clinical conditions, as well as numerous pathological and biological features, are analogous with NETs deleterious effects. Among NETs by-products implicated in COVID-19 pathogenesis, one of the most significant appears to be elastase, in accelerating virus entry and inducing hypertension, thrombosis and vasculitis. We postulate that severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) may evade innate immune response, causing uncontrolled NETs formation and multi-organ failure. In addition, we point to indicators that NETS-associated diseases are COVID-19 risk factors. Acknowledging that neutrophils are the principal origin of extracellular and circulating DNA release, we nonetheless, explain why targeting NETs rather than neutrophils themselves may in practice be a better strategy. This paper also offers an in-depth review of NET formation, function and pathogenic dysregulation, as well as of current and prospective future therapies to control NETopathies. As such, it enables us also to suggest new therapeutic strategies to fight COVID-19. In combination with or independent of the latest tested approaches, we propose the evaluation, in the short term, of treatments with DNase-1, with the anti-diabetic Metformin, or with drugs targeting elastase (i.e., Silvelestat). With a longer perspective, we also advocate a significant increase in research on the development of toll-like receptors (TLR) and C-type lectin-like receptors (CLEC) inhibitors, NET-inhibitory peptides, and on anti-IL-26 therapies.

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

Parasitology ◽  
2014 ◽  
Vol 141 (11) ◽  
pp. 1489-1498 ◽  
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.

scholarly journals Neutrophil Extracellular Traps are Involved in the Innate Immune Response to Infection with Leptospira

2015 ◽  
Vol 9 (7) ◽  
pp. e0003927 ◽  
Author(s):  
Emilia Scharrig ◽  
Agostina Carestia ◽  
María F. Ferrer ◽  
Maia Cédola ◽  
Gabriela Pretre ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Extracellular Traps

scholarly journals The Dual Role of Myeloperoxidase in Immune Response

2020 ◽  
Vol 21 (21) ◽  
pp. 8057 ◽  
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.

scholarly journals Corticosteroids and cellulose purification improve respectively the in vivo translation and vaccination efficacy of self-amplifying mRNAs

2020 ◽  
Author(s):  
Zifu Zhong ◽  
Séan Mc Cafferty ◽  
Lisa Opsomer ◽  
Haixiu Wang ◽  
Hanne Huysmans ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Biomedical Applications ◽  
Innate Immune ◽  
Type I ◽  
Type I Ifn ◽  
Therapeutic Platform ◽  
By Products

AbstractSynthetic mRNAs are an appealing therapeutic platform with multiple biomedical applications ranging from protein replacement therapy to vaccination. In comparison to conventional mRNA, synthetic self-amplifying mRNAs (sa-mRNAs) are gaining increased interest due to their higher and longer-lasting expression. However, sa-mRNAs also elicit an innate immune response, which may complicate the clinical translation of this platform. Approaches to reduce the innate immunity of sa-mRNAs have not been studied in detail. In this work we investigated the effect of several innate immune inhibitors and a novel cellulose-based mRNA purification approach on the type I interferon (IFN) response, translation and vaccination efficacy of our formerly developed sa-mRNA vaccine against Zika virus. Among the investigated inhibitors, we found that topical application of clobetasol at the sa-mRNA injection site was the most efficient in suppressing the type I IFN response and increasing the translation of sa-mRNA. However, clobetasol prevented the formation of antibodies against sa-mRNA encoded antigens and should therefore be avoided in a vaccination context. Residual dsRNA by-products of the in vitro transcription reaction are known inducers of immediate type I IFN responses. We additionally demonstrate drastic reduction of these dsRNA by-products upon cellulose-based purification, consequently reducing the innate immune response and improving sa-mRNA vaccination efficacy.

scholarly journals MODERN VIEWS ON THE ROLE OF NEUTROPHILS IN THE IMMUNE RESPONSE

2021 ◽  
Vol 67 (3) ◽  
pp. 75-86
Author(s):  
T.I. Gavrilenko ◽  
◽  
N.А. Rizhkova ◽  
O.M. Parkhomenko ◽  
E.V. Dovgan ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Functional Activity ◽  
Innate Immune ◽  
Vital Activity ◽  
First Line ◽  
Effector Cells ◽  
Extracellular Traps ◽  
Potential Biomarker

The review provides information on neutrophils, which are important effector cells of the innate immune response and form the first line of defence against infection. Issues of maturation and functional activity of cells are highlighted. The stages of the vital activity of neutrophils are shown – migration, chemotaxis, adhesion, oxygen explosion, absorption, degranulation, apoptosis. Special attention is paid to neutrophilic extracellular traps and the importance of myeloperoxidase. Today, these cells are increasingly viewed as a potential biomarker with specific treatments.

Oral Immune Activation by Disgust and Disease-Related Pictures

2015 ◽  
Vol 29 (3) ◽  
pp. 119-129 ◽  
Author(s):  
Richard J. Stevenson ◽  
Deborah Hodgson ◽  
Megan J. Oaten ◽  
Luba Sominsky ◽  
Mehmet Mahmut ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Negative Control ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Immune Markers ◽  
Before And After ◽  
Secondary Analyses ◽  
Image Set

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.

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