title: Colitogenic Bacteroides thetaiotaomicron Antigens Access Host Immune Cells in a Sulfatase-Dependent Manner via Outer Membrane Vesicles.
abstract: Microbes interact with the host immune system via several potential mechanisms. One essential step for each mechanism is the method by which intestinal microbes or their antigens access specific host immune cells. Using genetically susceptible mice (dnKO) that develop spontaneous, fulminant colitis, triggered by Bacteroides thetaiotaomicron (B. theta), we investigated the mechanism of intestinal microbial access under conditions that stimulate colonic inflammation. B. theta antigens localized to host immune cells through outer membrane vesicles (OMVs) that harbor bacterial sulfatase activity. We deleted the anaerobic sulfatase maturating enzyme (anSME) from B. theta, which is required for post-translational activation of all B. theta sulfatase enzymes. This bacterial mutant strain did not stimulate colitis in dnKO mice. Lastly, access of B. theta OMVs to host immune cells was sulfatase dependent. These data demonstrate that bacterial OMVs and associated enzymes promote inflammatory immune stimulation in genetically susceptible hosts.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA; Department of Pediatrics, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Hickey
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Kristine A
authors.initials: KA
authors.lastname: Kuhn
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Donermeyer
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA.
authors.forename: Nathan T
authors.initials: NT
authors.lastname: Porter
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, Box 440, 405 30 Gothenburg, Sweden.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Jin
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Cameron
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Haerin
authors.initials: H
authors.lastname: Jung
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Gerard E
authors.initials: GE
authors.lastname: Kaiko
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Wegorzewska
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Nicole P
authors.initials: NP
authors.lastname: Malvin
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA.
authors.forename: Robert W P
authors.initials: RW
authors.lastname: Glowacki
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, Box 440, 405 30 Gothenburg, Sweden.
authors.forename: Gunnar C
authors.initials: GC
authors.lastname: Hansson
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA. Electronic address: allen@pathology.wustl.edu.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Allen
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA. Electronic address: emartens@umich.edu.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Martens
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA. Electronic address: stappenb@pathology.wustl.edu.
authors.forename: Thaddeus S
authors.initials: TS
authors.lastname: Stappenbeck
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D001439:Bacteroides / Q000235:genetics / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000382:microbiology* / Q000473:pathology; D004195:Disease Models, Animal; D017353:Gene Deletion; D005798:Genes, Bacterial; D054884:Host-Pathogen Interactions; D051379:Mice; D022142:Secretory Vesicles / Q000201:enzymology* / Q000378:metabolism*; D013429:Sulfatases / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D013429:Sulfatases