TLR4 and infectious disease: In extracellular space, HMGB1 acts as a damaged associated molecule pattern (DAMP) and a late mediator of lethal endotoxemia and sepsis that contributes to the pathogenesis of inflammatory and infectious diseases by interacting with multiple receptors, including toll-like receptor 4 (TLR4), receptor of advanced glycation and end products (RAGE) [9, 10].