Intestinal mucins trigger immune responses upon recognition by dendritic cells via protein-carbohydrate interactions. We used a combination of structural， biochemical， biophysical， and cell-based approaches to decipher the specificity of the interaction between mucin glycans and mammalian lectins expressed in the gut， including galectin (Gal)-3 and C-type lectin receptors. Gal-3 differentially recognized intestinal mucins with different O-glycosylation profiles， as determined by mass spectrometry (MS). Modification of mucin glycosylation， via chemical treatment leading to a loss of terminal glycans， promoted the interaction of Gal-3 to poly- N-acetyllactosamine. Specific interactions were observed... More
Intestinal mucins trigger immune responses upon recognition by dendritic cells via protein-carbohydrate interactions. We used a combination of structural， biochemical， biophysical， and cell-based approaches to decipher the specificity of the interaction between mucin glycans and mammalian lectins expressed in the gut， including galectin (Gal)-3 and C-type lectin receptors. Gal-3 differentially recognized intestinal mucins with different O-glycosylation profiles， as determined by mass spectrometry (MS). Modification of mucin glycosylation， via chemical treatment leading to a loss of terminal glycans， promoted the interaction of Gal-3 to poly- N-acetyllactosamine. Specific interactions were observed between mucins and mouse dendritic cell-associated lectin (mDectin)-2 or specific intercellular adhesion molecule-grabbing nonintegrin-related-1 (SIGN-R1)， but not mDectin-1， using a cell-reporter assay， as also confirmed by atomic force spectroscopy. We characterized the N-glycosylation profile of mouse colonic mucin (Muc)-2 by MS and showed that the interaction with mDectin-2 was mediated by high-mannose N-glycans. Furthermore， we observed Gal-3 binding to the 3 C-type lectins by force spectroscopy. We showed that mDectin-1， mDectin-2， and SIGN-R1 are decorated by N-glycan structures that can be recognized by the carbohydrate recognition domain of Gal-3. These findings provide a structural basis for the role of mucins in mediating immune responses and new insights into the structure and function of major mammalian lectins.-Leclaire， C.， Lecointe， K.， Gunning， P. A.， Tribolo， S.， Kavanaugh， D. W.， Wittmann， A.， Latousakis， D.， MacKenzie， D. A.， Kawasaki， N.， Juge， N. Molecular basis for intestinal mucin recognition by galectin-3 and C-type lectins.
