Neutrophil Extracellular Traps Effectively Control Acute Chikungunya Virus Infection

Hiroki, Carlos Hiroji; Toller-Kawahisa, Juliana E; Fumagalli, Marcílio Jorge; Colón, David F.; Figueiredo, Luíz Tadeu Moraes; Fonseca, Bendito A. L. D.; Franca, Rafael Freitas Oliveira; Cunha, Fernando Q.

doi:10.3389/fimmu.2019.03108

Cited by 92 publications

(96 citation statements)

References 37 publications

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“…The triggered neutrophils produce reactive oxygen species (ROS) and other cytotoxic mediators, which may dampen the virus infection (51). Moreover, neutrophils are able to release neutrophil extracellular traps (NETs), which are a sticky web of DNA conjugated with antimicrobial enzymes (such as myeloperoxidase and histones), resulting in the capture and the killing of different pathogens, including viruses (52)(53)(54). On the other hand, lymphocytes did not show a significant decrease in the early stage of viral infection but significantly decreased in severe and critically ill patients (34).…”

Section: Discussionmentioning

confidence: 99%

Immune-Inflammatory Parameters in COVID-19 Cases: A Systematic Review and Meta-Analysis

et al. 2020

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Background: The recent outbreak of coronavirus disease 2019 (COVID-19) has been rapidly spreading on a global scale and poses a great threat to human health. Acute respiratory distress syndrome, characterized by a rapid onset of generalized inflammation, is the leading cause of mortality in patients with COVID-19. We thus aimed to explore the effect of risk factors on the severity of the disease, focusing on immune-inflammatory parameters, which represent the immune status of patients. Methods: A comprehensive systematic search for relevant studies published up to April 2020 was performed by using the PubMed, Web of Science, EMBASE, and China National Knowledge Internet (CNKI) databases. After extracting all available data of immune-inflammatory indicators, we statistically analyzed the risk factors of severe and non-severe COVID-19 patients with a meta-analysis. Results: A total of 4,911 patients from 29 studies were included in the final meta-analysis. The results demonstrated that severe patients tend to present with increased white blood cell (WBC) and neutrophil counts, neutrophil-lymphocyte ratio (NLR), procalcitonin (PCT), C-reaction protein (CRP), erythrocyte sedimentation rate (ESR), and Interleukin-6 (IL-6) and a decreased number of total lymphocyte and lymphocyte subtypes, such as CD4+ T lymphocyte and CD8+ T lymphocyte, compared to the non-severe patients. In addition, the WBC count>10 × 10 9 /L, lymphocyte count<1 × 10 9 /L, PCT>0.5 ng/mL, and CRP>10 mg/L were risk factors for disease progression in patients with COVID-19 (WBC count>10 × 10 9 /L: OR = 2.92, 95% CI: 1.96-4.35; lymphocyte count<1 × 10 9 /L: OR = 4.97, 95% CI: 3.53-6.99; PCT>0.5 ng/mL: OR = 6.33, 95% CI: 3.97-10.10; CRP>10 mg/L: OR = 3.51, 95% CI: 2.38-5.16). Furthermore, we found that NLR, as a novel marker of systemic inflammatory response, can also help predict clinical severity in patients with COVID-19 (OR = 2.50, 95% CI: 2.04-3.06). Conclusions: Immune-inflammatory parameters, such as WBC, lymphocyte, PCT, CRP, and NLR, could imply the progression of COVID-19. NLR has taken both the levels Feng et al. Immune-Inflammatory Parameters in COVID-19 of neutrophil and lymphocyte into account, indicating a more complete, accurate, and reliable inspection efficiency; surveillance of NLR may help clinicians identify high-risk COVID-19 patients at an early stage.

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Section: Discussionmentioning

confidence: 99%

Immune-Inflammatory Parameters in COVID-19 Cases: A Systematic Review and Meta-Analysis

et al. 2020

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“…Several stimuli trigger NETosis, including pathogen-associated molecular patterns, damage-associated molecular patterns, and inflammatory mediators, including cytokines and chemokines (Brinkmann et al, 2004;Keshari et al, 2012). There is also evidence that infection of neutrophils with several viruses triggered the formation of NETs (Saitoh et al, 2012;Funchal et al, 2015;Hiroki et al, 2020), which led us to investigate whether SARS-CoV-2 is able to directly promote NET release by human neutrophils. For that, neutrophils isolated from the blood of healthy controls were cultured in the presence of different multiplicities of infection (MOIs) of viable and inactivated SARS-CoV-2.…”

Section: Sars-cov-2 Replication Induces the Release Of Netsmentioning

confidence: 99%

“…Together, these results indicate that NETs might be a potential harmful mediator from neutrophils that cause lung epithelial cell damage during SARS-CoV-2 activation. Moreover, NETs could also activate different pattern recognition receptors, including TLR4 and 7, that mediate the release of inflammatory mediators, which in turn can amplify the direct effects of NETs in COVID-19 patients (Saitoh et al, 2012;Funchal et al, 2015;Hiroki et al, 2020).…”

Section: Sars-cov-2-activated Neutrophils Induce Lung Epithelial Cellmentioning

confidence: 99%

SARS-CoV-2–triggered neutrophil extracellular traps mediate COVID-19 pathology

Veras

Pontelli

Silva

et al. 2020

Journal of Experimental Medicine

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876

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Severe COVID-19 patients develop acute respiratory distress syndrome that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that neutrophil extracellular traps (NETs) have been described as important mediators of tissue damage in inflammatory diseases, we investigated whether NETs would be involved in COVID-19 pathophysiology. A cohort of 32 hospitalized patients with a confirmed diagnosis of COVID-19 and healthy controls were enrolled. The concentration of NETs was augmented in plasma, tracheal aspirate, and lung autopsies tissues from COVID-19 patients, and their neutrophils released higher levels of NETs. Notably, we found that viable SARS-CoV-2 can directly induce the release of NETs by healthy neutrophils. Mechanistically, NETs triggered by SARS-CoV-2 depend on angiotensin-converting enzyme 2, serine protease, virus replication, and PAD-4. Finally, NETs released by SARS-CoV-2–activated neutrophils promote lung epithelial cell death in vitro. These results unravel a possible detrimental role of NETs in the pathophysiology of COVID-19. Therefore, the inhibition of NETs represents a potential therapeutic target for COVID-19.

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“…In fact, it has been suggested that aberrant production of NETs might be implicated in the development of pathological outcomes, such as autoimmune diseases, cancer, thrombosis and tissue damage 42 . On the other hand, NETs have been shown to control the growth and propagation of a variety of pathogens, such as bacteria 1,23,39,43,44 , parasites 7,45,46 , fungi 2,[47][48][49] , and viruses 8,28,[50][51][52][53][54][55] .…”

Section: Discussionmentioning

confidence: 99%

Neutrophil extracellular traps from healthy donors and HIV-1-infected individuals restrict HIV-1 production in macrophages

Mojoli

Gonçalves

Temerozo

et al. 2020

Sci Rep

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Neutrophils release extracellular traps (NETs) after interaction with microorganisms and physiological or synthetic products. NETs consist of decondensed chromatin complexed with proteins, some of them with microbicidal properties. Because NETs can modulate the functioning of HIV-1 target cells, we aimed to verify whether they modify HIV-1 replication in macrophages. We found that exposure of HIV-1-infected macrophages to NETs resulted in significant inhibition of viral replication. The NET anti-HIV-1 action was independent of other soluble factors released by the activated neutrophils, but otherwise dependent on the molecular integrity of NETs, since NET-treatment with protease or DNase abolished this effect. NETs induced macrophage production of the anti-HIV-1 β-chemokines Rantes and MIP-1β, and reduced the levels of integrated HIV-1 DNA in the macrophage genome, which may explain the decreased virus production by infected macrophages. Moreover, the residual virions released by NET-treated HIV-1-infected macrophages lost infectivity. In addition, elevated levels of DNA-elastase complexes were detected in the plasma from HIV-1-infected individuals, and neutrophils from these patients released NETs, which also inhibited HIV-1 replication in in vitro infected macrophages. Our results reveal that NETs may function as an innate immunity mechanism able to restrain HIV-1 production in macrophages.

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Neutrophil Extracellular Traps Effectively Control Acute Chikungunya Virus Infection

Cited by 92 publications

References 37 publications

Immune-Inflammatory Parameters in COVID-19 Cases: A Systematic Review and Meta-Analysis

Immune-Inflammatory Parameters in COVID-19 Cases: A Systematic Review and Meta-Analysis

SARS-CoV-2–triggered neutrophil extracellular traps mediate COVID-19 pathology

Neutrophil extracellular traps from healthy donors and HIV-1-infected individuals restrict HIV-1 production in macrophages

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