SFTSV Infection Induces BAK/BAX-Dependent Mitochondrial DNA Release to Trigger NLRP3 Inflammasome Activation

Li, Shufen; Li, Hao; Zhang, Yulan; Xin, Qilin; Guan, Zhenqiong; Chen, Xi; Zhang, Xiao-Ai; Li, Xiaokun; Xiao, Gengfu; Lozach, Pierre‐Yves; Cui, Jun; Liu, Wei; Zhang, Leike; Peng, Ke

doi:10.1016/j.celrep.2020.02.105

Cited by 89 publications

(75 citation statements)

References 55 publications

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“…Activation of caspase-1 through the NLRP3 inflammasome is often involved in virus-induced IL-1β processing and secretion. 14 However, treatment with the caspase-1 inhibitor, VX-765, did not affect SARS-CoV-2-induced pro-IL-1β production or IL-1β processing and secretion (Fig. 2a, b ).…”

Section: Resultsmentioning

confidence: 87%

SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation

Zhang

Guan

et al. 2020

Sig Transduct Target Ther

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to respiratory illness and multi-organ failure in critically ill patients. Although the virus-induced lung damage and inflammatory cytokine storm are believed to be directly associated with coronavirus disease 2019 (COVID-19) clinical manifestations, the underlying mechanisms of virus-triggered inflammatory responses are currently unknown. Here we report that SARS-CoV-2 infection activates caspase-8 to trigger cell apoptosis and inflammatory cytokine processing in the lung epithelial cells. The processed inflammatory cytokines are released through the virus-induced necroptosis pathway. Virus-induced apoptosis, necroptosis, and inflammation activation were also observed in the lung sections of SARS-CoV-2-infected HFH4-hACE2 transgenic mouse model, a valid model for studying SARS-CoV-2 pathogenesis. Furthermore, analysis of the postmortem lung sections of fatal COVID-19 patients revealed not only apoptosis and necroptosis but also massive inflammatory cell infiltration, necrotic cell debris, and pulmonary interstitial fibrosis, typical of immune pathogenesis in the lung. The SARS-CoV-2 infection triggered a dual mode of cell death pathways and caspase-8-dependent inflammatory responses may lead to the lung damage in the COVID-19 patients. These discoveries might assist the development of therapeutic strategies to treat COVID-19.

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Section: Resultsmentioning

confidence: 87%

SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation

Zhang

Guan

et al. 2020

Sig Transduct Target Ther

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300

324

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“…138,139 Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) infection triggers the activation of BCL2 antagonist/killer 1 (BAK)/BCL2-associated X (BAX) signaling, leading to mitochondrial dysfunction and release of oxidized mtDNA that activates the NLRP3 inflammasome. 140 Furthermore, the mitochondrial phospholipid cardiolipin appears to be a signaling platform for autophagy, apoptosis, and inflammasome activation. 141 Cardiolipin binds directly to the LRR domain of NLRP3 and provides an activating signal for NLRP3 inflammasome complex assembly and activation.…”

Section: Spatiotemporal Activation Of the Nlrp3 Inflammasome Complexmentioning

confidence: 99%

An update on the regulatory mechanisms of NLRP3 inflammasome activation

et al. 2021

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The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is a multiprotein complex involved in the release of mature interleukin-1β and triggering of pyroptosis, which is of paramount importance in a variety of physiological and pathological conditions. Over the past decade, considerable advances have been made in elucidating the molecular mechanisms underlying the priming/licensing (Signal 1) and assembly (Signal 2) involved in NLRP3 inflammasome activation. Recently, a number of studies have indicated that the priming/licensing step is regulated by complicated mechanisms at both the transcriptional and posttranslational levels. In this review, we discuss the current understanding of the mechanistic details of NLRP3 inflammasome activation with a particular emphasis on protein-protein interactions, posttranslational modifications, and spatiotemporal regulation of the NLRP3 inflammasome machinery. We also present a detailed summary of multiple positive and/or negative regulatory pathways providing upstream signals that culminate in NLRP3 inflammasome complex assembly. A better understanding of the molecular mechanisms underlying NLRP3 inflammasome activation will provide opportunities for the development of methods for the prevention and treatment of NLRP3 inflammasome-related diseases.

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“…The oxidized mtDNA (Shimada et al, 2012) and the new synthesis of mtDNA (Zhong et al, 2018) have been verified to directly induce NLRP3 inflammasome activation during apoptosis. In severe fever with thrombocytopenia syndrome (SFTS) virus infection, the cytosolic mtDNA binds and triggers NLRP3 inflammasome activation resulting in SFTS disease progression and fatal outcome (Li et al, 2020). The mtROS/inflammasome pathway involves arsenic-induced hepatic insulin resistance (Jia et al, 2020) and ozone-induced chronic lung inflammation and emphysema (Wiegman et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Bibliometric Analysis of the Inflammasome and Pyroptosis in Brain

Chen

Guo

et al. 2021

Front. Pharmacol.

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Background: Considering the pivotal role of inflammasome/pyroptosis in biological function, we visually analyzed the research hotspots of inflammasome/pyroptosis related to the brain in this work through the method of bibliometrics from the Web of Science (WOS) Core database over the past two decades.Methods: Documents were retrieved from WOS Core Collection on October 16, 2020. The search terms and strategies used for the WOS database are as follow: # 1, “pyroptosis”; # 2, “pyroptotic”; # 3, “inflammasome”; # 4, “pyroptosome”; # 5 “brain”; # 6, “# 1” OR “# 2” OR “# 3” OR “# 4”; # 7, “# 5” AND “# 6”. We selected articles and reviews published in English from 2000 to 2020. Visualization analysis and statistical analysis were performed by VOSviewer 1.6.15 and CiteSpace 5.7. R2.Results: 1,222 documents were selected for analysis. In the approximately 20 years since the pyroptosis was first presented, the publications regarding the inflammasome and pyroptosis in brain were presented since 2005. The number of annual publications increased gradually over a decade, which are involved in this work, and will continue to increase in 2020. The most prolific country was China with 523 documents but the United States was with 16,328 citations. The most influential author was Juan Pablo de Rivero Vaccari with 27 documents who worked at the University of Miami. The bibliometric analysis showed that inflammasome/pyroptosis involved a variety of brain cell types (microglia, astrocyte, neuron, etc.), physiological processes, ER stress, mitochondrial function, oxidative stress, and disease (traumatic brain injuries, stroke, Alzheimer’s disease, and Parkinson’s disease).Conclusion: The research of inflammasome/pyroptosis in brain will continue to be the hotspot. We recommend investigating the mechanism of mitochondrial molecules involved in the complex crosstalk of pyroptosis and regulated cell deaths (RCDs) in brain glial cells, which will facilitate the development of effective therapeutic strategies targeting inflammasome/pyroptosis and large-scale clinical trials. Thus, this study presents the trend and characteristic of inflammasome/pyroptosis in brain, which provided a helpful bibliometric analysis for researchers to further studies.

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SFTSV Infection Induces BAK/BAX-Dependent Mitochondrial DNA Release to Trigger NLRP3 Inflammasome Activation

Cited by 89 publications

References 55 publications

SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation

SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation

An update on the regulatory mechanisms of NLRP3 inflammasome activation

Bibliometric Analysis of the Inflammasome and Pyroptosis in Brain

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