Figure 2.

Schematic diagram depicts the mechanism(s) by which HIV-1/HIV-1 Tat and drug abuse modulate the NLRP3 and NLRC5 inflammasome signaling in the microglial cells. HIV-1/HIV-1 proteins, and drugs of abuse co-operatively activate microglia via: a) downregulated expression of NLRC5 resulting in activation of NF-κB (signal 1), leading, in turn, to transcriptional upregulation of NLRP3, and IL1β, and b) induction of ROS-mediated mitochondrial dysfunction (signal 2), which, in turn, induces assembly of NLRP3 inflammasome, leading to increased cleavage and secretion of mature IL1β, ultimately culminating in neuroinflammation and ensuing inflammaging.