The Mannose Receptor (CD206) and Its Siblings-The Back Story

The Mannose Receptor (MR or CD206) was identified in alveolar macrophages following a series of in vivo clearance experiments using purified β glucuronidase, other lysosomal enzymes and neoglycoproteins as probes. The receptor was identified as a 180 kDa membrane protein and a c-DNA clone was isolated which revealed a type one membrane protein comprised of a N-terminal cysteine rich domain, a fibronectin type II domain and a series of 8 CTLDs or C-type lectin-like domains, one or more of which binds mannose, fucose and N-acetylglucosamine. Subsequently, three other family members were identified-Endo180, PLA2R and DEC-205. CD206 was among the first endocytosis receptors to be shown to recycle between an endosomal compartment and the plasma membrane. Numerous macrophage populations, and selected other cells, are now known to express CD206. Expression of CD206 is highly regulated and widely accepted as a marker for M2-like macrophages where it is highly expressed. A soluble form of CD206, sCD206, resulting from the proteolytic cleavage of membrane bound CD206, is found in extracellular fluids where it may be functional. CD206 may function in host defense via pathogen recognition, in antigen uptake and presentation, in regulating the quality of the extracellular environment and in cell signaling through its interaction with partner proteins. Recent work reveals CD206 as an excellent target for the delivery of therapeutics- drugs and vaccines - to macrophages and dendritic cells.