Abstract
Antibodies of the secretory IgA (SIgA) class comprise the first line of antigen-specific immune defense, preventing access of commensal and pathogenic microorganisms and their secreted products into the body proper. In addition to preventing infection, SIgA shapes the composition of the gut microbiome. SIgA is transported across intestinal epithelial cells into gut secretions by the polymeric immunoglobulin receptor (pIgR). The epithelial surface is protected by a thick network of mucus, which is composed of a dense, sterile inner layer and a loose outer layer that is colonized by commensal bacteria. Immunofluorescence microscopy of mouse and human colon tissues demonstrated that the SIgA co-localizes with gut bacteria in the outer mucus layer. Using mice genetically deficient for pIgR and/or mucin-2 (Muc2, the major glycoprotein of intestinal mucus), we found that Muc2 but not SIgA was necessary for excluding gut bacteria from the inner mucus layer in the colon. Our findings support a model whereby SIgA is anchored in the outer layer of colonic mucus through combined interactions with mucin proteins and gut bacteria, thus providing immune protection against pathogens while maintaining a mutually beneficial relationship with commensals.
Highlights
The human intestinal tract is home to some 100 trillion microorganisms, tenfold more than the total number of host cells throughout the body [1]
The ability of secretory IgA (SIgA) to associate with the epithelial surface of the colonic mucosa is critical for its dual roles of excluding pathogens and maintaining a mutually beneficial relationship with commensals
Current models suggest that SIgA adheres to the mucus layer by association of glycan side chains of secretory component (SC) with the heavily glycosylated mucin proteins [11,16,17]
Summary
The human intestinal tract is home to some 100 trillion microorganisms, tenfold more than the total number of host cells throughout the body [1]. These SIgA antibodies contribute to adaptive immunity via specific antibody activity and to innate immunity via glycan-mediated binding to gut bacteria [5,6] Together, these immune functions promote intestinal homeostasis by neutralizing potentially hazardous microbes, shaping the composition of the commensal microbiota, and preventing inappropriate inflammatory responses to microbial and food antigens [3]. We found that the SIgA is relatively absent from the inner mucus layer, and is instead found to be associated with gut bacteria in the outer mucus layer These findings have implications regarding the mechanisms through which SIgA provides immune protection in the colon, where its major function is to restrict entry of commensal bacteria into the body proper
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