Resumen de TLR sorting by Rab11 endosomes maintains intestinal epithelial-microbial homeostasis
Shiyan Yu, Yingchao Nie, Byron Knowles, Ryotaro Sakamori, Ewa Stypulkowski, Chirag Patel, Soumyashree Das, Veronique Douard, Ronaldo P. Ferraris, E. M. Bonder, James R. Goldenring, Y. Tony Ip, Nan Gao
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.
