Potential role of AIM2 inflammasome in SARS‐CoV‐2 infection

SARS‐CoV‐2 is the causative agent of coronavirus disease 2019 (COVID‐19). The disease presents different degrees of severity related to the antiviral response of the host. According to clinical manifestations, patients could show mild, moderate and severe COVID‐19. Regarding immunological aspects, an increased interferon (IFN) response in COVID‐19 patients with mild and moderate symptoms were observed;however, in severe COVID‐19, IFN response is decreased. Patients with severe COVID‐19 display a hyperinflammatory disorder that leads to acute respiratory distress syndrome. Interestingly, the expression and activation of AIM2, a receptor induced by IFN, play an important role in the onset of antiviral response. In this review, we discuss the possible role of AIM2 during SARS‐CoV‐2 infection. We summarize the studies reporting the expression and activity of proteins involved upstream and downstream of AIM2‐inflammasome activation, such as IFN, ASC, Caspase‐1, IL‐1β, IL‐18, free‐dsDNA, IFI16, as well as SARS‐CoV‐2 viral load, cell death in groups of COVID‐19 patients with different clinical outcomes to infer the possible contribution of AIM2 in antiviral response of SARS‐CoV‐2 infection.

Potential role of AIM2 inflammasome in SARS-CoV-2 infection

SARS-CoV-2 is the causative agent of coronavirus disease 2019 (COVID-19). The disease presents different degrees of severity related to the antiviral response of the host. According to clinical manifestations, patients could show mild, moderate and severe COVID-19. Regarding immunological aspects, an increased interferon (IFN) response in COVID-19 patients with mild and moderate symptoms were observed;however, in severe COVID-19, IFN response is decreased. Patients with severe COVID-19 display a hyperinflammatory disorder that leads to acute respiratory distress syndrome. Interestingly, the expression and activation of AIM2, a receptor induced by IFN, play an important role in the onset of antiviral response. In this review, we discuss the possible role of AIM2 during SARS-CoV-2 infection. We summarize the studies reporting the expression and activity of proteins involved upstream and downstream of AIM2-inflammasome activation, such as IFN, ASC, Caspase-1, IL-1 beta, IL-18, free-dsDNA, IFI16, as well as SARS-CoV-2 viral load, cell death in groups of COVID-19 patients with different clinical outcomes to infer the possible contribution of AIM2 in antiviral response of SARS-CoV-2 infection.

Expression profiling of inflammation-related genes including IFI-16, NOTCH2, CXCL8, THBS1 in COVID-19 patients.

The present study aimed to scrutinize the expression profile of inflammatory-related genes (IFI-16, NOTCH2, CXCL8, and THBS1) from acute to post-acute stage of this infectious epidemic. The current cross-sectional study consisted of 53 acute-phase COVID-19 patients and 53 healthy individuals between February and March 2021. The extraction of total RNA was performed from PBMC specimens and also expression level of selected genes (IFI-16, NOTCH2, CXCL8, and THBS1) was evaluated by real-time PCR. Subsequently, levels of these factors were re-measured six weeks after the acute phase to determine if the levels of chosen genes returned to normal after the acute phase of COVID-19. Receiver operating characteristic (ROC) curve was plotted to test potential of genes as a diagnostic biomarker. The expression levels of inflammatory-related genes were significantly different between healthy and COVID-19 subjects. Besides, a significant higher CXCL8 level was found in the acute-phase COVID-19 compared to post-acute-phase infection which may be able to be considered as a potential biomarker for distinguishing between the acute phases from the post-acute-phase status. Deregulation of the inflammatory-related genes in COVID-19 patients, especially CXCL-8, can be serving as potent biomarkers to manage the COVID-19 infection.

Detection of Viral Infections by Innate Immunity.

Pattern recognition receptors (PRRs) and inflammasomes are a key part of the anti-viral innate immune system as they detect conserved viral pathogen-associated molecular patterns (PAMPs). A successful host response to viral infections critically depend on the initial activation of PRRs by viruses, mainly by viral DNA and RNA. The signalling pathways activated by PRRs leads to the expression of pro-inflammatory cytokines, to recruit immune cells, and type I and type III interferons which leads to the induction of interferon stimulated genes (ISG), powerful virus restriction factors that establish the "antiviral state". Inflammasomes contribute to anti-viral responses through the maturation of interleukin (IL)-1 and IL-18 and through triggering pyroptotic cell death. The activity of the innate immune system along with the adaptive immune response normally leads to successful virus elimination, although disproportionate innate responses contribute to viral pathology. In this review we will discuss recent insights into the influence of PRR activation and inflammasomes on viral infections and what this means for the mammalian host. We will also comment on how specific PRRs and inflammasomes may be relevant to how SARS-CoV-2, the virus responsible for the current COVID-19 pandemic, interacts with host innate immunity.