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A Large Polysaccharide Produced by Helicobacter hepaticus Induces an Anti-inflammatory Gene Signature in Macrophages

Lookup NU author(s): Dr Fiona Cuskin, Dr Elisabeth Lowe



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2017 The Authors Interactions between the host and its microbiota are of mutual benefit and promote health. Complex molecular pathways underlie this dialog, but the identity of microbe-derived molecules that mediate the mutualistic state remains elusive. Helicobacter hepaticus is a member of the mouse intestinal microbiota that is tolerated by the host. In the absence of an intact IL-10 signaling, H. hepaticus induces an IL-23-driven inflammatory response in the intestine. Here we investigate the interactions between H. hepaticus and host immune cells that may promote mutualism, and the microbe-derived molecule(s) involved. Our results show that H. hepaticus triggers early IL-10 induction in intestinal macrophages and produces a large soluble polysaccharide that activates a specific MSK/CREB-dependent anti-inflammatory and repair gene signature via the receptor TLR2. These data identify a host-bacterial interaction that promotes mutualistic mechanisms at the intestinal interface. Further understanding of this pathway may provide novel prevention and treatment strategies for inflammatory bowel disease. Host-microbiota interactions are of mutual benefit, and chronic intestinal inflammation develops when this dialog is altered. Danne et al. identified a polysaccharide produced by Helicobacter hepaticus that induces a specific anti-inflammatory and repair program in macrophages by activating the TLR2/MSK/CREB pathway. Further understanding may provide prevention and treatment strategies for IBD.

Publication metadata

Author(s): Danne C, Ryzhakov G, Martinez-Lopez M, Ilott NE, Franchini F, Cuskin F, Lowe EC, Bullers SJ, Arthur JSC, Powrie F

Publication type: Article

Publication status: Published

Journal: Cell Host and Microbe

Year: 2017

Volume: 22

Issue: 6

Pages: 733-745.e5

Print publication date: 13/12/2017

Online publication date: 13/12/2017

Acceptance date: 06/10/2017

Date deposited: 07/02/2018

ISSN (print): 1931-3128

ISSN (electronic): 1934-6069

Publisher: Cell Press


DOI: 10.1016/j.chom.2017.11.002


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