TLR sorting by Rab11 endosomes maintains intestinal epithelial-microbial homeostasis.

Yu S, Nie Y, Knowles B, Sakamori R, Stypulkowski E, Patel C, Das S, Douard V, Ferraris RP, Bonder EM, Goldenring JR, Ip YT, Gao N
EMBO J. 2014 33 (17): 1882-95

PMID: 25063677 · PMCID: PMC4195784 · DOI:10.15252/embj.201487888

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.

© 2014 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

MeSH Terms (13)

Animals Drosophila Drosophila Proteins Endosomes Enterocytes Gene Deletion Homeostasis Intestinal Mucosa Mice Microbiota rab GTP-Binding Proteins Receptors, Immunologic Toll-Like Receptor 9

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