Altered mucosal homeostasis in mice lacking secretory antibodies

The mammalian gut is inhabited by a large and complex microbial community that lives in a mutualistic relationship with its host. Innate and adaptive mucosal defense mechanisms ensure a homeostatic relationship with this commensal microbiota. Secretory antibodies are generated from the active polymeric Ig receptor (pIgR)-mediated transport of IgA and IgM antibodies to the gut lumen and form the first line of adaptive immune defense of the intestinal mucosa. We probed mucosal homeostasis in pIgR knockout (KO) mice, which lack secretory antibodies. We found that in pIgR KO mice, colonic epithelial cells, the cell type most closely in contact with intestinal microbes, differentially expressed (>2-fold change) more than 200 genes compared with wild type mice, and upregulated the expression of anti-microbial peptides in a commensal-dependent manner. Detailed profiling of microbial communities based on 16S rRNA genes revealed differences in the commensal microbiota between pIgR KO and wild type mice. Furthermore, we found that pIgR KO mice showed increased susceptibility to dextran sulfate sodium (DSS)-induced colitis, and that this was driven by their conventional intestinal microbiota. In conclusion, secretory antibodies or the pIgR itself are required to maintain a stable commensal microbiota. In the absence of these humoral effector components, gut homeostasis is disturbed and the outcome of colitis significantly worsened. 4 groups: wild type mice treated with antibiotic (5 replicates), wild type mice left untreated (5 replicates), pIgR KO mice treated with antibiotic (6 replicates), and pIgR KO mice left untreated (6 replicates).