Editorial: The role of inflammasome in viral infection

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

“…COVID-19 exhibits a wide spectrum of clinical presentations, ranging from asymptomatic cases to severe pneumonia or even death [1,2]. In serious cases of COVID-19, a "cytokine storm" can be observed, which is triggered by excessive and uncontrolled activation of the inflammasome, thereby alluding to the crucial involvement of the inflammasome in the exacerbation of this devasting disease [5][6][7][8][9]22]. Despite the impact of COVID-19 on public health, we still do not fully understand how the inflammatory response influences disease prognosis.…”

“…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].…”