Figure 5.

AIM2 and Pyrin inflammasome activation. (A) AIM2 inflammasome activation occurs in response to microbial or self-DNA. Cytosolic bacteria induce the production of type I IFNs which drive the expression of GBPs and IRGB10, targeting bacterial and vacuolar membranes for destruction. Bacterial DNA released into the cytoplasm to initiate AIM2 activation.In contrast, DNA viruses can activate AIM2 without type I IFN signaling. AIM2 also recognizes host cytoplasmic double-stranded DNA (dSDNA) leaked from nuclear or mitochondrial damage caused by Ionizing radiation chemotherapeutics. Upon binding to DNA, AIM2 participate in the following recruitment of ASC and pro-caspase-1,resulting in AIM2 inflammasome-caspase-1-mediated pyroptosis. (B) Under normal conditions, human and murine pyrin is phosphorylated by the Ras homolog family member A (RhoA) effector kinases, protein kinase N1/2 (PKN1/2) that keep pyrin in an inactive state. Bacterial toxins can inhibit RhoA activity and subsequent PKN1/2 phosphorylation, leading to the dephosphorylation of pyrin,which maintain it active status and recruits ASC and pro-caspase-1. Ultimately, active caspase-1 Inducts pyroptosis.