Abstract

Innate and adaptive mucosal defense mechanisms ensure a homeostatic relationship with the large and complex mutualistic gut microbiota. Dimeric IgA and pentameric IgM are transported across the intestinal epithelium via the epithelial polymeric Ig receptor (pIgR) and provide a significant portion of the first line of natural or adaptive antibody-mediated immune defense of the intestinal mucosa. We found that colonic epithelial cells from pIgR KO mice differentially expressed (more than twofold change) more than 200 genes compared with cells from WT mice, and upregulated the expression of antimicrobial 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 WT mice. Furthermore, we found that pIgR KO mice showed increased susceptibility to dextran sulfate sodium-induced colitis, and that this was driven by their conventional intestinal microbiota. Thus, in the absence of pIgR, the stability of the commensal microbiota is disturbed, gut homeostasis is compromised, and the outcome of colitis is significantly worsened.

Links

Publisher Full Text

Authors

Reikvam DH, Derrien M, Islam R, Erofeev A, Grcic V, Sandvik A, Gaustad P, Meza-Zepeda LA, Jahnsen FL, Smidt H, Johansen FE

Institution

Department of Pathology and Centre for Immune Regulation, University of Oslo and Oslo University Hospital - Rikshospitalet, Oslo, Norway.

Source

European journal of immunology 42:11 2012 Nov pg 2959-70

MeSH

Adaptive Immunity
Animals
Antimicrobial Cationic Peptides
Colitis
Epithelial Cells
Female
Gene Expression Profiling
Gene Expression Regulation
Intestinal Mucosa
Male
Metagenome
Mice
Mice, Inbred BALB C
Mice, Knockout
Oligonucleotide Array Sequence Analysis
RNA
Random Allocation
Receptors, Polymeric Immunoglobulin
Reverse Transcriptase Polymerase Chain Reaction
Specific Pathogen-Free Organisms

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22865203