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

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

doi:10.1016/j.chom.2017.11.002

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

Camille Danne (Lead / Corresponding author), Grigory Ryzhakov, Maria Martínez-López, Nicholas Edward Ilott, Fanny Franchini, Fiona Cuskin, Elisabeth C. Lowe, Samuel J. Bullers, J. Simon C. Arthur, Fiona Powrie

Cell Signalling and Immunology

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Abstract

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.

Original language	English
Pages (from-to)	733-745.e5
Number of pages	18
Journal	Cell Host & Microbe
Volume	22
Issue number	6
Early online date	13 Dec 2017
DOIs	https://doi.org/10.1016/j.chom.2017.11.002
Publication status	Published - 13 Dec 2017

Keywords

Journal article
Inflammatory bowel disease
Host-microbe interactions
Mutualism
Helicobacter hepaticus
Macrophage
Anti-inflammatory gene signature
Polysaccharide
TLR2
CREB
MSK1/2

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Final published version, 3.8 MBLicence: CC BY

Arthur, Simon
- Cell Signalling and Immunology - Professor of Immune Signalling
Person: Academic

Cite this

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

abstract = "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.",

keywords = "Journal article, Inflammatory bowel disease , Host-microbe interactions , Mutualism , Helicobacter hepaticus, Macrophage , Anti-inflammatory gene signature , Polysaccharide, TLR2 , CREB, MSK1/2",

author = "Camille Danne and Grigory Ryzhakov and Maria Mart{\'i}nez-L{\'o}pez and Ilott, {Nicholas Edward} and Fanny Franchini and Fiona Cuskin and Lowe, {Elisabeth C.} and Bullers, {Samuel J.} and Arthur, {J. Simon C.} and Fiona Powrie",

note = "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.",

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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 -

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

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Arthur, Simon

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