TLR4 and Sepsis: AIM2 can be activated by high-mobility group box 1 (HMGB1) via Toll-like receptors (TLR) 2, TLR4, and RAGE/NF-κB pathways in macrophages, and inhibition of AIM2 inflammasome activation can restrain macrophages from releasing IL-1β and IL-18 and protect mice against polymicrobial sepsis and septic death (Xie et al., 2016; Li and Lu, 2020).