Flagellin hypervariable region determines symbiotic properties of commensal Escherichia coli strains

Autor: Annika Bender, Tobias A. Oelschlaeger, Martin Schaller, Anna Lange, Jan K. Maerz, Julia-Stefanie Frick, Hans Yao, Lena Michaelis, Andrea I. Schäfer, Mehari Tesfazgi Mebrhatu, Brianna Ball, Raphael Parusel, Samuel Wagner, Alexander N.R. Weber, Alex Steimle, Sina Beier, Ingo B. Autenrieth, Kerstin Gronbach, Birgit Fehrenbacher, Sarah Menz, Hanna-Christine Löw, Thomas Hagemann, David Voehringer
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Glycobiology
medicine.disease_cause
Biochemistry
Immune Receptors
Mice
0302 clinical medicine
Intestinal mucosa
Medizinische Fakultät
Microbial Physiology
Natural Resources
Medicine and Health Sciences
Bacterial Physiology
Intestinal Mucosa
Biology (General)
Toll-like Receptors
Glucans
Escherichia coli Infections
Immune System Proteins
General Neuroscience
Escherichia coli Proteins
Interleukin
Animal Models
Colitis
Intestines
Experimental Organism Systems
Water Resources
Female
Anatomy
General Agricultural and Biological Sciences
Symbiotic bacteria
Signal Transduction
Research Article
QH301-705.5
Immunology
Mouse Models
Gastroenterology and Hepatology
Biology
Research and Analysis Methods
Microbiology
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Immune system
Model Organisms
Polysaccharides
medicine
Escherichia coli
Animals
ddc:610
Symbiosis
Dextran
General Immunology and Microbiology
Inflammatory Bowel Disease
Ecology and Environmental Sciences
Biology and Life Sciences
Proteins
Bacteriology
Cell Biology
medicine.disease
Hypervariable region
Mice
Inbred C57BL
Gastrointestinal Tract
Disease Models
Animal
Toll-Like Receptor 5
Species Interactions
030104 developmental biology
biology.protein
Animal Studies
Digestive System
030217 neurology & neurosurgery
Flagellin
Zdroj: PLoS Biology, Vol 17, Iss 6, p e3000334 (2019)
PLoS Biology
Popis: Escherichia coli represents a classical intestinal gram-negative commensal. Despite this commensalism, different E. coli strains can mediate disparate immunogenic properties in a given host. Symbiotic E. coli strains such as E. coli Nissle 1917 (EcN) are attributed beneficial properties, e.g., promotion of intestinal homeostasis. Therefore, we aimed to identify molecular features derived from symbiotic bacteria that might help to develop innovative therapeutic alternatives for the treatment of intestinal immune disorders. This study was performed using the dextran sodium sulphate (DSS)-induced colitis mouse model, which is routinely used to evaluate potential therapeutics for the treatment of Inflammatory Bowel Diseases (IBDs). We focused on the analysis of flagellin structures of different E. coli strains. EcN flagellin was found to harbor a substantially longer hypervariable region (HVR) compared to other commensal E. coli strains, and this longer HVR mediated symbiotic properties through stronger activation of Toll-like receptor (TLR)5, thereby resulting in interleukin (IL)-22–mediated protection of mice against DSS-induced colitis. Furthermore, using bone-marrow–chimeric mice (BMCM), CD11c+ cells of the colonic lamina propria (LP) were identified as the main mediators of these flagellin-induced symbiotic effects. We propose flagellin from symbiotic E. coli strains as a potential therapeutic to restore intestinal immune homeostasis, e.g., for the treatment of IBD patients.
A flagellum renders bacteria motile, but this study reveals another property important for symbiosis: the hypervariable region of Escherichia coli flagellin strongly determines activation of TLR5, mediating benefits for the host such as protection against colitis.
Databáze: OpenAIRE
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