What discriminates danger signals from pathogens with that of damage to tissues

The immune system protects against infection by pathogenic microorganisms, but it also recognizes when the body has been injured. Burns, radiation exposure, and bruises all involve the immune system when responding to damaged tissue. Which signaling pathways recognize tissue damage and keep the resulting inflammatory response from getting out of hand? Patten recognition receptors, which recognize pathogens or components of injured cells (danger), trigger activation of the innate immune system. Whether and how the host distinguishes between danger- versus pathogen-associated molecular patterns remains unresolved. In seminal paper in Science (Vol. 323. no. 5922, pp. 1722 - 1725, March 2009), Chen and colleagues demonstrated an unique mechanisms by which the body differentiates between self- and non-self signals during danger.
They that CD24-deficient mice exhibit increased susceptibility to danger- (DAMPs) but not pathogen-associated molecular patterns (PAMPs). CD24 associates with high mobility group box 1 (HMGB1), heat shock protein 70 (HSP70), and heat shock protein 90 (HSP90), negatively regulates their stimulatory activity, and inhibits nuclear factor-kappa B (NF-B) activation. This occurs at least in part through CD24 association with Siglec-10 in humans or Siglec-G in mice. Our results reveal that the CD24-Siglec-G pathway protects the host against a lethal response to pathological cell death and discriminates danger- versus pathogen-associated molecular patterns. Through association with and inhibition of the molecules that are released after tissue damage, CD24 and Siglec-G protected mice from an otherwise lethal inflammatory response.