HMGB1, a DAMP that Likes DCs HMGB1, a sentinel for nucleic-acid-mediated response in DCs. During microbial infection, the activation of innate immune responses by DNA and RNA is essential to protective immune responses and is mediated by the NH2  COOH  A box  B box  Acidic tail   1  79  89  163  186  215  DNA binding domain  DNA binding domain   150  183  RAGE-binding domain   28  44  NLS1   179  185  NLS2  C106   TLR4 binding site   Proinflammatory  cytokine-domain   89  108   100  189  202 transmembrane TLRs and cytosolic receptors. 23 TLRs belong to a family of pattern recognition receptors (PRRs) that have essential roles in innate immunity. They are a class of single-membrane-spanning receptors that have the ability to recognize structurally conserved molecules from bacteria. Engagement of TLRs activates the immune response.