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

Publication date: 13 December 2017
Source:Cell Host & Microbe, Volume 22, Issue 6
Author(s): Camille Danne, Grigory Ryzhakov, Maria Martínez-López, Nicholas Edward Ilott, Fanny Franchini, Fiona Cuskin, Elisabeth C. Lowe, Samuel J. Bullers, J. Simon C. Arthur, Fiona Powrie
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.

Graphical abstract

Teaser

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.


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