Lung Inflammasome Activation in SARS-CoV-2 Post-Mortem Biopsies

Carstens, Lucas Baena; D'Amico, Raíssa Campos; Moura, Karen Fernandes de; Castro, Eduardo Morais de; Oliveira, Flávia Centenaro de; Barbosa, Giovanna Silva; Silva, Guilherme Vieira Cavalcante da; Brenny, Isadora Drews; D’Agostini, Júlio César Honório; Hlatchuk, Elisa Carolina; Lima, Sabrina Pissette de; Martins, Ana Paula Camargo; Deus, Marina de Castro; Klein, Carolline Konzen; Benevides, Ana Paula Kubaski; Nagashima, Seigo; Souza, Cleber Machado de; Pinho, Ricardo A.; Baena, Cristina Pellegrino; Noronha, Lúcia de

doi:10.3390/ijms232113033

Cited by 11 publications

(11 citation statements)

References 57 publications

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“…SARS-CoV-2 infection triggered NLRP3 inflammasome activation and increased the levels of caspase-1, IL-1b and IL-18 in the lung tissues, which precipitated systemic inflammation and exacerbated lung immunopathology in vivo (60,90). Blockade of NLRP3 inflammasome via genetic knockout and specific inhibitor MCC950 apparently restrained NLRP3 inflammasome activation induced by SARS-CoV-2 infection (90).…”

Section: Therapeutic Potential Of Inflammasome-targeting Intervention...mentioning

confidence: 99%

Inflammasomes: a rising star on the horizon of COVID-19 pathophysiology

Wang

Chang

et al. 2023

Front. Immunol.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a contagious respiratory virus that is the cause of the coronavirus disease 2019 (COVID-19) pandemic which has posed a serious threat to public health. COVID-19 is characterized by a wide spectrum of clinical manifestations, ranging from asymptomatic infection to mild cold-like symptoms, severe pneumonia or even death. Inflammasomes are supramolecular signaling platforms that assemble in response to danger or microbial signals. Upon activation, inflammasomes mediate innate immune defense by favoring the release of proinflammatory cytokines and triggering pyroptotic cell death. Nevertheless, abnormalities in inflammasome functioning can result in a variety of human diseases such as autoimmune disorders and cancer. A growing body of evidence has showed that SARS-CoV-2 infection can induce inflammasome assembly. Dysregulated inflammasome activation and consequent cytokine burst have been associated with COVID-19 severity, alluding to the implication of inflammasomes in COVID-19 pathophysiology. Accordingly, an improved understanding of inflammasome-mediated inflammatory cascades in COVID-19 is essential to uncover the immunological mechanisms of COVID-19 pathology and identify effective therapeutic approaches for this devastating disease. In this review, we summarize the most recent findings on the interplay between SARS-CoV-2 and inflammasomes and the contribution of activated inflammasomes to COVID-19 progression. We dissect the mechanisms involving the inflammasome machinery in COVID-19 immunopathogenesis. In addition, we provide an overview of inflammasome-targeted therapies or antagonists that have potential clinical utility in COVID-19 treatment.

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Section: Therapeutic Potential Of Inflammasome-targeting Intervention...mentioning

confidence: 99%

Inflammasomes: a rising star on the horizon of COVID-19 pathophysiology

Wang

Chang

et al. 2023

Front. Immunol.

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“…NLRP3 assembly with consequent activation of caspase-1 and downstream consequences like increased active TNF-alpha, IL-1beta and IL-18 are increased in the lungs of fatal COVID-19 cases [ 53 , 56 ]. Dapsone has been shown to decrease these in a variety of clinical and rodent studies [ 3 , 57 , 58 , 59 , 60 ].…”

Section: Discussionmentioning

confidence: 99%

Dapsone Lowers Neutrophil to Lymphocyte Ratio and Mortality in COVID-19 Patients Admitted to the ICU

Kanwar¹,

Khattak²,

Kast³

2022

IJMS

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Some physicians use dapsone as part of the standard treatment of severe COVID-19 patients entering the ICU, though some do not. To obtain an indication of whether dapsone is helping or not, we undertook a retrospective chart review of 29 consecutive ICU COVID-19 patients receiving dapsone and 30 not receiving dapsone. As we previously reported, of those given dapsone, 9/29 (30%) died, while of those not given dapsone, 18/30 (60%) died. We looked back on that data set to determine if there might be basic laboratory findings in these patients that might give an indication of a mechanism by which dapsone was acting. We found that the neutrophil-to-lymphocyte ratio decreased in 48% of those given dapsone and in 30% of those not given dapsone. We concluded that dapsone might be lowering that ratio. We then reviewed collected data on neutrophil related inflammation pathways on which dapsone might act as presented here. As this was not a controlled study, many variables prevent drawing any conclusions from this work; a formal, randomized controlled study of dapsone in severe COVID-19 is warranted.

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“…However, uncontrolled NLRP3 inflammasome can trigger excessive IL-1β and other inflammatory cytokines, leading to the cell death by pyroptosis ( 47 , 48 ). Excessive mature IL-1β can stimulate systemic inflammatory responses, resulting in the release of large amounts of cytokines, including IL-6, tumor necrosis factor-α (TNFα), interferon (IFN)-α, IFN-β.…”

Section: Innate Immune Systemmentioning

confidence: 99%

Innate and adaptive immunity to SARS-CoV-2 and predisposing factors

et al. 2023

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The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), has affected all countries worldwide. Although some symptoms are relatively mild, others are still associated with severe and even fatal clinical outcomes. Innate and adaptive immunity are important for the control of SARS-CoV-2 infections, whereas a comprehensive characterization of the innate and adaptive immune response to COVID-19 is still lacking and the mechanisms underlying immune pathogenesis and host predisposing factors are still a matter of scientific debate. Here, the specific functions and kinetics of innate and adaptive immunity involved in SARS-CoV-2 recognition and resultant pathogenesis are discussed, as well as their immune memory for vaccinations, viral-mediated immune evasion, and the current and future immunotherapeutic agents. We also highlight host factors that contribute to infection, which may deepen the understanding of viral pathogenesis and help identify targeted therapies that attenuate severe disease and infection.

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Lung Inflammasome Activation in SARS-CoV-2 Post-Mortem Biopsies

Cited by 11 publications

References 57 publications

Inflammasomes: a rising star on the horizon of COVID-19 pathophysiology

Inflammasomes: a rising star on the horizon of COVID-19 pathophysiology

Dapsone Lowers Neutrophil to Lymphocyte Ratio and Mortality in COVID-19 Patients Admitted to the ICU

Innate and adaptive immunity to SARS-CoV-2 and predisposing factors

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