title: A pathobiont of the microbiota balances host colonization and intestinal inflammation.
abstract: The gastrointestinal tract harbors a diverse microbiota that has coevolved with mammalian hosts. Though most associations are symbiotic or commensal, some resident bacteria (termed pathobionts) have the potential to cause disease. Bacterial type VI secretion systems (T6SSs) are one mechanism for forging host-microbial interactions. Here we reveal a protective role for the T6SS of Helicobacter hepaticus, a Gram-negative bacterium of the intestinal microbiota. H. hepaticus mutants with a defective T6SS display increased numbers within intestinal epithelial cells (IECs) and during intestinal colonization. Remarkably, the T6SS directs an anti-inflammatory gene expression profile in IECs, and CD4+ T cells from mice colonized with T6SS mutants produce increased interleukin-17 in response to IECs presenting H. hepaticus antigens. Thus, the H. hepaticus T6SS limits colonization and intestinal inflammation, promoting a balanced relationship with the host. We propose that disruption of such balances contributes to human disorders such as inflammatory bowel disease and colon cancer.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Chow
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: sarkis@caltech.edu.
authors.forename: Sarkis K
authors.initials: SK
authors.lastname: Mazmanian
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology; D015169:Colony Count, Microbial; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004847:Epithelial Cells / Q000382:microbiology; D020869:Gene Expression Profiling; D055786:Gene Knockout Techniques; D044923:Helicobacter hepaticus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D020381:Interleukin-17 / Q000096:biosynthesis; D046911:Macromolecular Substances / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D020381:Interleukin-17; D046911:Macromolecular Substances; D008565:Membrane Proteins