Immune and inflammatory pathways in the brain are activated in AUD (13). In gene expression profiling of postmortem human brains, a connection between immune responses and AUD has been established; genes exhibiting significant expression differences are enriched in pathways related to interferon signaling (14). Interferons—with their antiviral, antiproliferative, and immunomodulatory effects—play a critical role in human innate and adaptive immune responses during chronic alcohol exposure (14). Using human induced pluripotent stem cells (iPSCs) as a model system, it has been shown that ethanol exposure activates NLRP3 inflammasome in human iPSCs and iPSC-derived neural progenitor cells (15). Microglia are the primary resident immune cells in the brain (16) and have a variety of receptors that enable them to sense alterations in their microenvironment, leading to changes in transcription, morphology, and function (17, 18). Brain microglial cells play multifaceted roles, including the regulation of inflammation, participation in phagocytosis (19), and engagement in specialized brain-specific functions through interactions with neurons, such as the modulation of neurotransmission and synaptic pruning (20, 21). Exposure to ethanol triggers microglia activation, leading to morphological changes and heightened
