TLR sorting by Rab11 endosomes maintains intestinal epithelial-microbial homeostasis

• Shiyan Yu ^[1] ; Yingchao Nie ^[2] ; Byron Knowles ^[3] ; Ryotaro Sakamori ^[1] ; Ewa Stypulkowski ^[1] ; Chirag Patel ^[4] ; Soumyashree Das ^[1] ; Veronique Douard ^[4] ; Ronaldo P Ferraris ^[4] ; Edward M Bonder ^[1] ; James R Goldenring ^[3] ; Yicktung Tony Ip ^[2] ; Nan Gao ^[1]
  1. [1] Rutgers University

     Rutgers University

     City of New Brunswick, Estados Unidos

     
  2. [2] University of Massachusetts Medical School

     University of Massachusetts Medical School

     City of Worcester, Estados Unidos

     
  3. [3] Vanderbilt University Medical Center

     Vanderbilt University Medical Center

     Estados Unidos

     
  4. [4] 4 Department of Pharmacology and Physiology, Rutgers-New Jersey Medical School Newark, NJ, USA

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 33, Nº. 17, 2014, págs. 1882-1895
• Idioma: inglés
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• Resumen

  • Compartmentalization of Toll-like receptors (TLRs) in intestinal epithelial cells (IECs) regulates distinct immune responses to microbes; however, the specific cellular machinery that controls this mechanism has not been fully identified. Here we provide genetic evidences that the recycling endosomal compartment in enterocytes maintains a homeostatic TLR9 intracellular distribution, supporting mucosal tolerance to normal microbiota. Genetic ablation of a recycling endosome resident small GTPase, Rab11a, a gene adjacent to a Crohn's disease risk locus, in mouse IECs and in Drosophila midgut caused epithelial cell-intrinsic cytokine production, inflammatory bowel phenotype, and early mortality. Unlike wild-type controls, germ-free Rab11a-deficient mouse intestines failed to tolerate the intraluminal stimulation of microbial agonists. Thus, Rab11a endosome controls intestinal host-microbial homeostasis at least partially via sorting TLRs.