NLRP3, the inflammasome and COVID-19 infection

Yin, Maureen; Marrone, Laura; Peace, Christian G.; O’Neill, Luke A.J.

doi:10.1093/qjmed/hcad011

Cited by 13 publications

(7 citation statements)

References 59 publications

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“…76,77 NLRP3 inflammasome, which was the key regulator to activate body macrophage reaction, played an important role in COVID-19 and the potential clinical treatment targeting it is being studied. 78 Moreover, OA development was associated with macrophage polarization and macrophage was transformed from resting to activating. In this process, macrophage M1 that promotes inflammation would increase while the number of anti-inflammation macrophage M2 would reduce.…”

Section: Discussionmentioning

confidence: 99%

“…It was widely reported that macrophage infiltration occurred in patients' airways and would lead to lung injury 76,77 . NLRP3 inflammasome, which was the key regulator to activate body macrophage reaction, played an important role in COVID‐19 and the potential clinical treatment targeting it is being studied 78 . Moreover, OA development was associated with macrophage polarization and macrophage was transformed from resting to activating.…”

Section: Discussionmentioning

confidence: 99%

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Bioinformatics and system biology analysis revealed the crosstalk between COVID‐19 and osteoarthritis

Lai,

Jiang,

Liao

et al. 2023

Immunity Inflam & Disease

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BackgroundThe global coronavirus disease 2019 (COVID‐19) outbreak has significantly impacted public health. Moreover, there has been an association between the incidence and severity of osteoarthritis (OA) and the onset of COVID‐19. However, the optimal diagnosis and treatment strategies for patients with both diseases remain uncertain. Bioinformatics is a novel approach that may help find the common pathology between COVID‐19 and OA.MethodsDifferentially expressed genes (DEGs) were screened by R package “limma.” Functional enrichment analyses were performed to find key biological functions. Protein–protein interaction (PPI) network was constructed by STRING database and then Cytoscape was used to select hub genes. External data sets and OA mouse model validated and identified the hub genes in both mRNA and protein levels. Related transcriptional factors (TF) and microRNAs (miRNAs) were predicted with miRTarBase and JASPR database. Candidate drugs were obtained from Drug Signatures database. The immune infiltration levels of COVID‐19 and OA were evaluated by CIBERSORT and scRNA‐seq.ResultsA total of 74 common DEGs were identified between COVID‐19 and OA. Receiver operating characteristic curves validated the effective diagnostic values (area under curve > 0.7) of four hub genes (matrix metalloproteinases 9, ATF3, CCL4, and RELA) in both the training and validation data sets of COVID‐19 and OA. Quantitative polymerase chain reaction and Western Blot showed significantly higher hub gene expression in OA mice than in healthy controls. A total of 84 miRNAs and 28 TFs were identified to regulate the process of hub gene expression. The top 10 potential drugs were screened including “Simvastatin,” “Hydrocortisone,” and “Troglitazone” which have been proven by Food and Drug Administration. Correlated with hub gene expression, Macrophage M0 was highly expressed while Natural killer cells and Mast cells were low in both COVID‐19 and OA.ConclusionFour hub genes, disease‐related miRNAs, TFs, drugs, and immune infiltration help to understand the pathogenesis and perform further studies, providing a potential therapy target for COVID‐19 and OA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bioinformatics and system biology analysis revealed the crosstalk between COVID‐19 and osteoarthritis

Lai,

Jiang,

Liao

et al. 2023

Immunity Inflam & Disease

View full text Add to dashboard Cite

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“…Because recent airway administration of TLR agonists resulted in elevated lung levels of IL-1β and IL-18, we next investigated whether inflammasome-related pathways contribute to innate control of viral replication in SCV2 infection. Indeed, both inflammasome activation and pyroptotic cell death have been implicated in SCV2 pathogenesis [89][90][91][92] . Similar to observations made in an AAV-hACE2 mouse model of SCV2 infection 93 that the inflammatory changes in the lung microenvironment prior to SCV2 infection might also extend to changes in lung epithelial cells (ECs), the primary target and reservoir of SCV2 replication 94,95 .…”

Section: Pulmonary Scv2 Replication Is Restricted By Nucleic Acid Sen...mentioning

confidence: 99%

The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication

Baker,

Bohrer,

Castro

et al. 2024

Preprint

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SARS-CoV-2 infection leads to vastly divergent clinical outcomes ranging from asymptomatic infection to fatal disease. Co-morbidities, sex, age, host genetics and vaccine status are known to affect disease severity. Yet, how the inflammatory milieu of the lung at the time of SARS-CoV-2 exposure impacts the control of viral replication remains poorly understood. We demonstrate here that immune events in the mouse lung closely preceding SARS-CoV-2 infection significantly impact viral control and we identify key innate immune pathways required to limit viral replication. A diverse set of pulmonary inflammatory stimuli, including resolved antecedent respiratory infections with S. aureus or influenza, ongoing pulmonary M. tuberculosis infection, ovalbumin/alum-induced asthma or airway administration of defined TLR ligands and recombinant cytokines, all establish an antiviral state in the lung that restricts SARS-CoV-2 replication upon infection. In addition to antiviral type I interferons, the broadly inducible inflammatory cytokines TNFα and IL-1 precondition the lung for enhanced viral control. Collectively, our work shows that SARS-CoV-2 may benefit from an immunologically quiescent lung microenvironment and suggests that heterogeneity in pulmonary inflammation that precedes or accompanies SARS-CoV-2 exposure may be a significant factor contributing to the population-wide variability in COVID-19 disease outcomes.

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“…This is, perhaps, responsible for peripheral lymphopenia in severe COVID-19 patients. The role of inflammasome is also related to development of severe inflammation in COVID-19 patients [ 111 , 112 , 113 , 114 , 115 , 116 ]. In addition to this, attention should be focused on the initial failure or suboptimal induction of innate immunity in the host during initial exposure to SARS-CoV-2 in order to allow for the development of proper insights into the cellular and molecular mechanisms underlying severe COVID-19.…”

Section: Possible Mechanisms Underlying Failure Of Containing Sars-co...mentioning

confidence: 99%

Cellular and Molecular Mechanisms of Pathogenic and Protective Immune Responses to SARS-CoV-2 and Implications of COVID-19 Vaccines

2023

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has devastated the world with coronavirus disease 2019 (COVID-19), which has imparted a toll of at least 631 million reported cases with 6.57 million reported deaths. In order to handle this pandemic, vaccines against SARS-CoV-2 have been developed and billions of doses of various vaccines have been administered. In the meantime, several antiviral drugs and other treatment modalities have been developed to treat COVID-19 patients. At the end of the day, it seems that anti-SARS-CoV-2 vaccines and newly developed antiviral drugs may be improved based on various new developments. COVID-19 represents a virus-induced, immune-mediated pathological process. The severity of the disease is related to the nature and properties of the host immune responses. In addition, host immunity plays a dominant role in regulating the extent of COVID-19. The present reality regarding the role of anti-SARS-CoV-2 vaccines, persistence of SARS-CoV-2 infection even three years after the initiation of the pandemic, and divergent faces of COVID-19 have initiated several queries among huge populations, policy makers, general physicians, and scientific communities. The present review aims to provide some information regarding the molecular and cellular mechanisms underlying SARS-CoV-2 infection.

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NLRP3, the inflammasome and COVID-19 infection

Cited by 13 publications

References 59 publications

Bioinformatics and system biology analysis revealed the crosstalk between COVID‐19 and osteoarthritis

Bioinformatics and system biology analysis revealed the crosstalk between COVID‐19 and osteoarthritis

The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication

Cellular and Molecular Mechanisms of Pathogenic and Protective Immune Responses to SARS-CoV-2 and Implications of COVID-19 Vaccines

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