CD24-Siglec G/10 discriminates danger- from pathogen-associated molecular patterns

Abstract

It is now well accepted that the innate immune system recognizes both damage (or danger)- and pathogen-associated molecular patterns (DAMP and PAMP, respectively) through pattern recognition receptors, such as Toll-like receptors (TLR) and/or Nod-like receptors (NLR). Less clear are whether and how the response to PAMP and DAMP are regulated differentially. The answers may reveal whether the primary goal of the immune system is to defend against infections or to alert the host of tissue injuries. We demonstrated recently that the host response to DAMP is controlled by a DAMP-CD24-Siglec axis. Here we propose a key role for the CD24-Siglec pathway in discriminating between DAMPs and PAMPs.

Figure 1

The CD24-Siglec G (mouse) or -Siglec 10 (human) pathway discriminates between Pathogen-Associated Molecular Patterns (PAMPs) from Danger-Associated Molecular Patterns (DAMPs) by selective repression of the host response to DAMPs. We propose that DAMPs (but not PAMPs) bring CD24-Siglec G/10 into the proximity of TLR/NLR, thus allowing Siglec G/10-associated phosphatases such as SHP1 to repress the DAMP-initiated TLR/NLR signaling. Dysfunction of this pathway might contribute to the etiology of autoimmune disease.