fig6

Figure 6. Schematic representation of the role of microglial NLRP3 on neuronal synaptodendritic injury via exosomes. Exposure of microglia (BV2 or HPM) with HIV-1 Tat results in the activation of NLRP3 inflammasome complex, whichleads to the production of IL-1β and microglial activation. Thereafter, these NLRP3 and IL1β can be packaged in the exosomes and released by the microglia. These exosomes carrying NLRP3/IL1β upon uptake by the neurons result in alteration of synaptic proteins (PSD95, vGLUT1, GAD65, Gephyrin) and dendritic injury (change in the spine- numbers and sub-types). Overall, these microglial EVs carrying NLRP3 cargoes can cause synaptodendritic injury resulting in HAND in patients via microglia-neuron cross talk. NLRP3: NOD-, LRR- and pyrin domain-containing protein 3; ASC: apoptosis-associated speck-like protein; IL 1β: interleukin 1β; PSD95: postsynaptic density protein 95; vGLUT1: vesicular glutamate transporters; GAD65: glutamic acid decarboxylase; Tat: trans-activator of transcription.