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

Abstract

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.

The laboratory parameters in predicting the severity and death of COVID-19 patients: Future pandemic readiness strategies

“…Various immune cells, such as macrophages, dendritic cells, and T lymphocytes, are activated. Dysregulation of these immune responses can lead to a cytokine storm, which is characterized by the excessive production of pro-inflammatory cytokines [ 23 , 24 ].…”

Inflammasome-Related Genetic Polymorphisms as Severity Biomarkers of COVID-19

“…Despite advances in understanding the predictors of the vaccine humoral response, the biological predictors of COVID-19 exacerbation have still not been fully defined. In this context, the aggravation of COVID-19 has a relevant relationship with the overproduction of proinflammatory cytokines, as well as with the recruitment of proinflammatory macrophages and granulocytes that cause the so-called "cytokine storm" [5][6][7][8][9][10][11]. This "cytokine storm" is frequently triggered by the activation of inflammasomes; protein complexes formed in the cytosol in response to several stimuli, which exert their function through an innate immune receptor; an adaptor protein (an adapter apoptosis-associated, speck-like protein containing a caspase recruitment domain (CARD)); and an effector enzyme (caspase-1 (CASP-1)) [5][6][7][8][9].…”

“…In this context, the aggravation of COVID-19 has a relevant relationship with the overproduction of proinflammatory cytokines, as well as with the recruitment of proinflammatory macrophages and granulocytes that cause the so-called "cytokine storm" [5][6][7][8][9][10][11]. This "cytokine storm" is frequently triggered by the activation of inflammasomes; protein complexes formed in the cytosol in response to several stimuli, which exert their function through an innate immune receptor; an adaptor protein (an adapter apoptosis-associated, speck-like protein containing a caspase recruitment domain (CARD)); and an effector enzyme (caspase-1 (CASP-1)) [5][6][7][8][9]. Several inflammasomes have been involved in viral infections, some of the most relevant being the nucleotide oligomerization domain leucinerich repeat (NLR) pyrin-domain containing protein 3 (NLRP3), the NLR pyrin-domain containing protein 1 (NLRP1), or the NLR Family CARD containing 4 (NLRC4).…”

“…When an inflammasome is stimulated, an assembly is induced and recruits CASP-1, which converts pro-interleukin (IL)-1β and pro-IL-18 to their active forms. Consequently, these cytokines trigger the inflammatory response during the viral infection [5][6][7][8][9]12]. This biological process is tightly controlled by several factors such as macrophage migration inhibitory factor (MIF) and the autophagy-related 16-like 1 (ATG16L1), which have recently been highlighted by their important role in regulating NLRP3 inflammasome activation, as well as by the release of IL-1b and IL-18 [13,14].…”

“…Interestingly, studies have proven that SARS-CoV-2 represents a pathogen-associated molecular pattern that is able to trigger inflammasome activation, whereby the overexuberant inflammasome response has emerged as a relevant predisposing factor for disease severity and poor clinical outcome in COVID-19 patients [5][6][7][8][9]. In particular, NLRP3 and NLRP1 inflammasome activation-as well as the components of its signaling, i.e., CASP1, IL-1β, and IL-18, etc.-show a relationship with the inflammatory factors and disease progression in patients with COVID-19 [5][6][7][8][9][15][16][17][18]. In fact, some inflammasome inhibitors that exist for other non-infectious diseases have the potential to be used to treat severe SARS-CoV-2 complications [7].…”