Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease

American Association for the Advancement of Science (AAAS) - Tập 352 Số 6289 - Trang 1116-1120 - 2016
Hiutung Chu1, Arya Khosravi1, Indah P. Kusumawardhani1, Alice H. K. Kwon1, A.C. Vasconcelos2, Larissa D. Cunha3, A. Mayer4, Yue Shen1, Wei‐Li Wu1, Amal Kambal4, Stephan R. Targan5, Ramnik J. Xavier6, Peter B. Ernst2, Douglas R. Green3, Dermot McGovern5, Herbert W. Virgin4, Sarkis K. Mazmanian1
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
2Center for Veterinary Sciences and Comparative Medicine, University of California, San Diego, San Diego, CA 92093, USA.
3Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA
4Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
5F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
6Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA

Tóm tắt

Genes and microbes converge in colitis Both host genetics and intestinal microbes probably contribute to a person's overall susceptibility to inflammatory bowel disease (IBD). The human gut microbe Bacteroides fragilis produces immunomodulatory molecules that it releases via outer membrane vesicles (OMVs). These molecules can protect mice from experimentally induced colitis. Chu et al. now find that OMV-mediated protection from colitis requires Atg16l1 and Nod2 genes whose human orthologs are associated with an increased risk for developing IBD. OMVs trigger an ATG16L1 and NOD2–dependent noncanonical autophagy pathway in dendritic cells (DCs). OMV-primed DCs, in turn, induce regulatory T cells in the intestine that protect against colitis. Science , this issue p. 1116

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American Association for the Advancement of Science (AAAS)

Tập 352 Số 6289

1116-1120

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