title: Recognition of gram-positive intestinal bacteria by hybridoma- and colostrum-derived secretory immunoglobulin A is mediated by carbohydrates.
abstract: Humans live in symbiosis with 10(14) commensal bacteria among which >99% resides in their gastrointestinal tract. The molecular bases pertaining to the interaction between mucosal secretory IgA (SIgA) and bacteria residing in the intestine are not known. Previous studies have demonstrated that commensals are naturally coated by SIgA in the gut lumen. Thus, understanding how natural SIgA interacts with commensal bacteria can provide new clues on its multiple functions at mucosal surfaces. Using fluorescently labeled, nonspecific SIgA or secretory component (SC), we visualized by confocal microscopy the interaction with various commensal bacteria, including Lactobacillus, Bifidobacteria, Escherichia coli, and Bacteroides strains. These experiments revealed that the interaction between SIgA and commensal bacteria involves Fab- and Fc-independent structural motifs, featuring SC as a crucial partner. Removal of glycans present on free SC or bound in SIgA resulted in a drastic drop in the interaction with gram-positive bacteria, indicating the essential role of carbohydrates in the process. In contrast, poor binding of gram-positive bacteria by control IgG was observed. The interaction with gram-negative bacteria was preserved whatever the molecular form of protein partner used, suggesting the involvement of different binding motifs. Purified SIgA and SC from either mouse hybridoma cells or human colostrum exhibited identical patterns of recognition for gram-positive bacteria, emphasizing conserved plasticity between species. Thus, sugar-mediated binding of commensals by SIgA highlights the currently underappreciated role of glycans in mediating the interaction between a highly diverse microbiota and the mucosal immune system.
authors: R&D Laboratory of the Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon, 1011 Lausanne, Switzerland.
authors: Amandine
authors: A
authors: Mathias
authors: Blaise
authors: B
authors: Corthésy
mesh_terms: D020816:Amino Acid Motifs; D002241:Carbohydrates / Q000737:chemistry*; D003126:Colostrum / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D019281:Dimerization; D006023:Glycoproteins / Q000737:chemistry; D006031:Glycosylation; D006094:Gram-Positive Bacteria / Q000378:metabolism*; D006801:Humans; D006825:Hybridomas / Q000378:metabolism* / Q000382:microbiology; D007071:Immunoglobulin A, Secretory / Q000378:metabolism*; D007128:Immunoglobulin Fragments / Q000737:chemistry; D007422:Intestines / Q000382:microbiology*; D007778:Lactobacillus / Q000378:metabolism; D018613:Microscopy, Confocal / Q000379:methods; D011134:Polysaccharides / Q000737:chemistry
chemical_list: D002241:Carbohydrates; D006023:Glycoproteins; D007071:Immunoglobulin A, Secretory; D007128:Immunoglobulin Fragments; D011134:Polysaccharides