HMGB1 and infection: Although initially discovered as receptors for pathogens, TLRs have been found to respond to endogenous agonists such as HMGB1 that are not related to infections.6,14 Recent findings have also revealed that astrocyte and neuron activation induces TLRs and other innate immune signaling receptors that can contribute to the initiation and propagation of innate immune responses.15–17 Pro-inflammatory signaling has emerged as a key mechanism contributing to brain responses to alcohol, and progressive changes during cycles of alcohol exposure may contribute to the development of AUD.