TY - JOUR
T1 - Flagellin hypervariable region determines symbiotic properties of commensal escherichia coli strains
AU - Steimle, Alex
AU - Menz, Sarah
AU - Bender, Annika
AU - Ball, Brianna
AU - Weber, Alexander N.R.
AU - Hagemann, Thomas
AU - Lange, Anna
AU - Maerz, Jan K.
AU - Parusel, Raphael
AU - Michaelis, Lena
AU - Schäfer, Andrea
AU - Yao, Hans
AU - Löw, Hanna Christine
AU - Beier, Sina
AU - Mebrhatu, Mehari Tesfazgi
AU - Gronbach, Kerstin
AU - Wagner, Samuel
AU - Voehringer, David
AU - Schaller, Martin
AU - Fehrenbacher, Birgit
AU - Autenrieth, Ingo B.
AU - Oelschlaeger, Tobias A.
AU - Frick, Julia Stefanie
N1 - Publisher Copyright:
© 2019 Steimle et al.
PY - 2019/6
Y1 - 2019/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85069235223&partnerID=8YFLogxK
U2 - 10.1371/journal.pbio.3000334
DO - 10.1371/journal.pbio.3000334
M3 - Article
C2 - 31206517
AN - SCOPUS:85069235223
SN - 1544-9173
VL - 17
JO - PLoS Biology
JF - PLoS Biology
IS - 6
M1 - e3000334
ER -