Epithelial-microbial crosstalk in polymeric Ig receptor deficient mice

被引:89
作者
Reikvam, Dag Henrik [2 ,3 ]
Derrien, Muriel [4 ]
Islam, Rejoanoul [2 ,3 ,4 ]
Erofeev, Alexander [2 ,3 ]
Grcic, Vedrana [2 ,3 ]
Sandvik, Anders [2 ,3 ]
Gaustad, Peter [5 ]
Meza-Zepeda, Leonardo A. [6 ,7 ]
Jahnsen, Frode L. [2 ,3 ]
Smidt, Hauke [4 ]
Johansen, Finn-Eirik [1 ,2 ,3 ]
机构
[1] Natl Hosp Norway, Oslo Univ Hosp, Dept Pathol, N-0424 Oslo, Norway
[2] Univ Oslo, Dept Pathol, Oslo, Norway
[3] Univ Oslo, Ctr Immune Regulat, Oslo, Norway
[4] Wageningen Univ, Microbiol Lab, Wageningen, Netherlands
[5] Univ Oslo, Inst Microbiol, Oslo, Norway
[6] Norwegian Radium Hosp, Oslo Univ Hosp, Dept Tumor Biol, Oslo, Norway
[7] Univ Oslo, Dept Mol Biosci, Norwegian Microarray Consortium, Oslo, Norway
基金
欧盟第七框架计划;
关键词
Antimicrobial peptide; Colitis; Polymeric Ig receptor; GUT MICROBIOTA; IMMUNE-RESPONSES; INTESTINAL MICROBIOTA; SECRETORY ANTIBODIES; IMMUNOGLOBULIN RECEPTOR; MAINTAIN HOMEOSTASIS; COLITIS; DISEASE; INFLAMMATION; ENVIRONMENT;
D O I
10.1002/eji.201242543
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:2959 / 2970
页数:12
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