Letter to the Glyco-Forum: Since there are PAMPs and DAMPs, there must be SAMPs? Glycan "self-associated molecular patterns" dampen innate immunity, but pathogens can mimic them

Abstract

The ∼500-million-year-old adaptive immune system detects foreign (“non-self”) epitopes via B cell-derived antibodies and/or T cell receptor interactions with major histocompatibility complex (MHC)/peptide complexes (Hedrick 2004). Cells of the more ancient innate immune system display receptors that detect foreign glycans, for example, fungal glycan recognition by the macrophage mannose receptor (Stahl and Ezekowitz 1998) or by circulating collectins and pentraxins (Bottazzi et al. 2010). The latter field was revolutionized by definition of “pathogen-associated molecular patterns” (PAMPs; Medzhitov and Janeway 1997), microbial products that can be detected by pattern recognition receptors (PRRs), particularly the Toll-like receptors (TLRs; Beutler 2009), Nod-like receptors (Davis et al. 2011) and dendritic cell receptors such as C-type lectins (Geijtenbeek et al. 2004). Many PAMPs are glycoconjugates (e.g., bacterial lipo-oligosaccharides) or glycan-based polymers (e.g., bacterial peptidoglycans), including bacterial DNA or viral RNA (which are (deoxy)ribose-based polymers). The innate immune system also recognizes “danger-associated molecular patterns” (DAMPs; Matzinger 2002; Chen and Nunez 2010), molecules released during tissue damage, such as heat-shock proteins, high mobility group box 1 (Lotze and Tracey 2005), hyaluronan (HA) fragments (Taylor and Gallo 2006), glycosaminoglycan (GAG)-bearing matrix proteoglycans (Moreth et al. 2010) and certain crystals (Martinon et al. 2009), all of which originate from damaged host cells or matrices. Signals initiated by DAMPs and PAMPs are transduced via similar pathways, activating innate immune inflammatory responses.