Flagellin hypervariable region determines symbiotic properties of commensal Escherichia coli strains

PLoS Biol. 2019 Jun 17;17(6):e3000334. doi: 10.1371/journal.pbio.3000334. eCollection 2019 Jun.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis / chemically induced
  • Colitis / immunology
  • Disease Models, Animal
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Escherichia coli Infections / microbiology
  • Escherichia coli Proteins / genetics
  • Female
  • Flagellin / genetics*
  • Flagellin / metabolism
  • Intestinal Mucosa
  • Intestines
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Signal Transduction / immunology
  • Symbiosis / genetics*
  • Symbiosis / physiology
  • Toll-Like Receptor 5 / metabolism

Substances

  • Escherichia coli Proteins
  • Tlr5 protein, mouse
  • Toll-Like Receptor 5
  • Flagellin

Grant support

This work was supported by Deutsches Zentrum für Infektionsforschung (German Center for Infection Research, http://www.dzif.de/en/), Deutsche Forschungsgemeinschaft (DFG) GRK1708 (http://www.dfg.de/gefoerderte_projekte/programme_und_projekte/listen/projektdetails/index.jsp?id=174858087), Deutsche Forschungsgemeinschaft (DFG) SFB685 (http://gepris.dfg.de/gepris/projekt/13799719). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.