The intestinal microbiota has a critical role in immune system and metabolic homeostasis, but it must be tolerated by the host to avoid inflammatory responses that can damage the epithelial barrier separating the host from the luminal contents1,2,3,4,5,6. Breakdown of this regulation and the resulting inappropriate immune response to commensals are thought to lead to the development of inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis7. We proposed that the intestinal immune system is instructed by the microbiota to limit responses to luminal antigens. Here we demonstrate in mice that, at steady state, the microbiota inhibits the transport of both commensal and pathogenic bacteria from the lumen to a key immune inductive site, the mesenteric lymph nodes (MLNs). However, in the absence of Myd88 or under conditions of antibiotic-induced dysbiosis, non-invasive bacteria were trafficked to the MLNs in a CCR7-dependent manner, and induced both T-cell responses and IgA production. Trafficking was carried out by CX3CR1hi mononuclear phagocytes, an intestinal-cell population previously reported to be non-migratory8. These findings define a central role for commensals in regulating the migration to the MLNs of CX3CR1hi mononuclear phagocytes endowed with the ability to capture luminal bacteria, thereby compartmentalizing the intestinal immune response to avoid inflammation.
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We thank H. Yue and J. Hall for comments on the manuscript and members of the Littman laboratory for their suggestions. We thank the NYU Histology Core, which is supported in part by grant 5P30CA016087-32 from the National Cancer Institute. Supported by the American Cancer Society and National Institutes of Health (NIH) T32 CA009161 (G.E.D.), NIH T32 DK083256-02 (R.S.L.), Human Frontier Science Program Long-Term Fellowship (B.B.), NIH R01AI085166 (S.R.S.) and the Howard Hughes Medical Institute (D.R.L.).
The authors declare no competing financial interests.
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Diehl, G., Longman, R., Zhang, JX. et al. Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX3CR1hi cells. Nature 494, 116–120 (2013). https://doi.org/10.1038/nature11809
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