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

TY - JOUR

T1 - A Large Polysaccharide Produced by Helicobacter hepaticus Induces an Anti-inflammatory Gene Signature in Macrophages

AU - Danne, Camille

AU - Ryzhakov, Grigory

AU - Martínez-López, Maria

AU - Ilott, Nicholas Edward

AU - Franchini, Fanny

AU - Cuskin, Fiona

AU - Lowe, Elisabeth C.

AU - Bullers, Samuel J.

AU - Arthur, J. Simon C.

AU - Powrie, Fiona

N1 - F.F. was supported by Cancer Research UK (OCRC-DPhil13-FF) and N.E.I. by the Kennedy Trust (KENN 15 16 03). M.M.-L. received a fellowship from the Spanish Ministry of Education, Culture, and Sport. This work was funded by the Wellcome Trust UK (095688/Z/11/Z), an ERC grant (Advanced Grant Ares(2013)3687660), and the Fondation Louis Jeantet.

PY - 2017/12/13

Y1 - 2017/12/13

N2 - 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.

AB - 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.

KW - Journal article

KW - Inflammatory bowel disease

KW - Host-microbe interactions

KW - Mutualism

KW - Helicobacter hepaticus

KW - Macrophage

KW - Anti-inflammatory gene signature

KW - Polysaccharide

KW - TLR2

KW - CREB

KW - MSK1/2

U2 - 10.1016/j.chom.2017.11.002

DO - 10.1016/j.chom.2017.11.002

M3 - Article

C2 - 29241040

SN - 1931-3128

VL - 22

SP - 733-745.e5

JO - Cell Host & Microbe

JF - Cell Host & Microbe

IS - 6

ER -