HMGB1 and Sepsis: It is worth noting that while pathogens trigger immune activation, it is well understood that endogenous molecules released upon tissue damage and/or cellular disruption (e.g., high mobility group protein B1 [HMGB1], S100 proteins, and heat shock proteins) are similarly capable of activating the immune system through PRRs resulting in a systemic response indistinguishable from sepsis (reviewed in [10]).