title: Genetic and Metabolic Signals during Acute Enteric Bacterial Infection Alter the Microbiota and Drive Progression to Chronic Inflammatory Disease.
abstract: Chronic inflammatory disorders are thought to arise due to an interplay between predisposing host genetics and environmental factors. For example, the onset of inflammatory bowel disease is associated with enteric proteobacterial infection, yet the mechanistic basis for this association is unclear. We have shown previously that genetic defiency in TLR1 promotes acute enteric infection by the proteobacteria Yersinia enterocolitica. Examining that model further, we uncovered an altered cellular immune response that promotes the recruitment of neutrophils which in turn increases metabolism of the respiratory electron acceptor tetrathionate by Yersinia. These events drive permanent alterations in anti-commensal immunity, microbiota composition, and chronic inflammation, which persist long after Yersinia clearence. Deletion of the bacterial genes involved in tetrathionate respiration or treatment using targeted probiotics could prevent microbiota alterations and inflammation. Thus, acute infection can drive long term immune and microbiota alterations leading to chronic inflammatory disease in genetically predisposed individuals.
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Karishma
authors.initials: K
authors.lastname: Kamdar
authors.affiliation: Department of Medicine, Section of Gastroenterology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Samira
authors.initials: S
authors.lastname: Khakpour
authors.affiliation: College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; Department of Food Science and Technology, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Medicine, Section of Gastroenterology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Leone
authors.affiliation: Argonne National Laboratory, Argonne, IL 60439, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Brulc
authors.affiliation: Department of Medicine, Section of Gastroenterology, University of Chicago, Chicago, IL 60637, USA; Department of Pediatrics Section of Pediatric Gastroenterology, Hepatology, & Nutrition, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mangatu
authors.affiliation: Department of Medicine, Section of Gastroenterology, University of Chicago, Chicago, IL 60637, USA; Argonne National Laboratory, Argonne, IL 60439, USA.
authors.forename: Dionysios A
authors.initials: DA
authors.lastname: Antonopoulos
authors.affiliation: Department of Medicine, Section of Gastroenterology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Eugene B
authors.initials: EB
authors.lastname: Chang
authors.affiliation: Department of Medicine, Section of Gastroenterology, University of Chicago, Chicago, IL 60637, USA; Department of Pediatrics Section of Pediatric Gastroenterology, Hepatology, & Nutrition, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Stacy A
authors.initials: SA
authors.lastname: Kahn
authors.affiliation: Department of Medicine, Section of Gastroenterology, University of Chicago, Chicago, IL 60637, USA; Department of Pediatrics Section of Pediatric Gastroenterology, Hepatology, & Nutrition, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Kirschner
authors.affiliation: Department of Food Science and Technology, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Glenn
authors.initials: G
authors.lastname: Young
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: william.depaolo@med.usc.edu.
authors.forename: R William
authors.initials: RW
authors.lastname: DePaolo
mesh_terms: D000818:Animals; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051194:Toll-Like Receptor 1 / Q000235:genetics / Q000276:immunology; D015009:Yersinia Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D015008:Yersinia enterocolitica / Q000502:physiology*
chemical_list: D051194:Toll-Like Receptor 1