The Antibacterial Lectin RegIIIγ Promotes the Spatial Segregation of Microbiota and Host in the Intestine
Abstract
The mammalian intestine is home to ~100 trillion bacteria that perform important metabolic functions for their hosts. The proximity of vast numbers of bacteria to host intestinal tissues raises the question of how symbiotic host-bacterial relationships are maintained without eliciting potentially harmful immune responses. Here, we show that RegIIIγ, a secreted antibacterial lectin, is essential for maintaining a ~50-micrometer zone that physically separates the microbiota from the small intestinal epithelial surface. Loss of host-bacterial segregation in RegIIIγ−/− mice was coupled to increased bacterial colonization of the intestinal epithelial surface and enhanced activation of intestinal adaptive immune responses by the microbiota. Together, our findings reveal that RegIIIγ is a fundamental immune mechanism that promotes host-bacterial mutualism by regulating the spatial relationships between microbiota and host.
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Published In
Science
Volume 334 | Issue 6053
14 October 2011
14 October 2011
Copyright
Copyright © 2011, American Association for the Advancement of Science.
Submission history
Received: 14 June 2011
Accepted: 26 August 2011
Published in print: 14 October 2011
Acknowledgments
Acknowledgments: We thank A. DeFranco for the Myd88fl/fl mice, R. Medzhitov for the FLAG-MyD88 transgene, and A. Mobley for assistance with flow cytometry. This work was supported by NIH R01 DK070855 (L.V.H.), a Crohn's and Colitis Foundation of America Fellowship Award (S.V.), the Human Microbiome Project Data Analysis and Coordination Center (O.K.), a Packard Fellowship in Science and Engineering (R.L.), a Hartwell Foundation investigator award (R.L.), a Beckman Young Investigator award (R.L.), a Burroughs Wellcome Foundation New Investigators in the Pathogenesis of Infectious Diseases Award (L.V.H.), and the Howard Hughes Medical Institute (L.V.H.). The data reported in this paper are tabulated in the main text and the supporting online material, and the sequencing data have been deposited in RG-RAST (accession no. MGP135).
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