Human MUC2 mucin inhibits the antimicrobial activity of β‐defensin 2

Abstract

The intestinal epithelium is layered by a barrier composed of MUC2 mucin produced by goblet cells and β‐defensin 2, an inducible peptide produced by epithelial cells that exhibits antimicrobial and chemotactic activity. Bacteria infections and Ulcerative colitis and Crohn's diseases are associated with less MUC2 and altered defensin expression. In this study, we quantified the interaction between MUC2 mucin and β‐defensins. Human colonic mucin co‐incubated with β‐defensin 2 impaired defensin antimicrobial activities against Escherichia coli. However, addition of mucin 10–30 minutes following bacterial incubation with β‐defensin 2 did not alter antimicrobial activity. Mucin protective function on bacteria was partially abrogated by digesting the mucin terminal sialic acid residues with neuraminidases and oxidizing carbohydrate residues with sodium metaperiodate. Expression of murine β‐defensin 4 mRNA, an orthologue of human β‐defensin 2, was constitutively increased in the colons of mice deficient in MUC2 (Muc2−/−) and in dextran sodium sulfate induced colitis. These studies suggest that MUC2 abrogates the antimicrobial effect of β‐defensin in the intestinal mucosa by binding bacteria and therefore, mucin may shape the normal microflora by limiting β‐defensin antimicrobial activity. In contrast, β‐defensins are up regulated during mucosal damage when the mucus barrier is breached.