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

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)733-745.e5
Number of pages18
JournalCell Host & Microbe
Volume22
Issue number6
Early online date13 Dec 2017
DOIs
Publication statusPublished - 13 Dec 2017

Fingerprint

Helicobacter hepaticus
Polysaccharides
Anti-Inflammatory Agents
Macrophages
Interleukin-10
Genes
Interleukin-23
Toll-Like Receptor 2
Symbiosis
Microbiota
Insurance Benefits
Inflammatory Bowel Diseases
Intestines

Keywords

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

Cite this

Danne, C., Ryzhakov, G., Martínez-López, M., Ilott, N. E., Franchini, F., Cuskin, F., ... Powrie, F. (2017). A Large Polysaccharide Produced by Helicobacter hepaticus Induces an Anti-inflammatory Gene Signature in Macrophages. Cell Host & Microbe, 22(6), 733-745.e5. https://doi.org/10.1016/j.chom.2017.11.002
Danne, Camille ; Ryzhakov, Grigory ; Martínez-López, Maria ; Ilott, Nicholas Edward ; Franchini, Fanny ; Cuskin, Fiona ; Lowe, Elisabeth C. ; Bullers, Samuel J. ; Arthur, J. Simon C. ; Powrie, Fiona. / A Large Polysaccharide Produced by Helicobacter hepaticus Induces an Anti-inflammatory Gene Signature in Macrophages. In: Cell Host & Microbe. 2017 ; Vol. 22, No. 6. pp. 733-745.e5.
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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.",
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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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Danne, C, Ryzhakov, G, Martínez-López, M, Ilott, NE, Franchini, F, Cuskin, F, Lowe, EC, Bullers, SJ, Arthur, JSC & Powrie, F 2017, 'A Large Polysaccharide Produced by Helicobacter hepaticus Induces an Anti-inflammatory Gene Signature in Macrophages', Cell Host & Microbe, vol. 22, no. 6, pp. 733-745.e5. https://doi.org/10.1016/j.chom.2017.11.002

A Large Polysaccharide Produced by Helicobacter hepaticus Induces an Anti-inflammatory Gene Signature in Macrophages. / Danne, Camille (Lead / Corresponding author); Ryzhakov, Grigory; Martínez-López, Maria; Ilott, Nicholas Edward; Franchini, Fanny; Cuskin, Fiona; Lowe, Elisabeth C.; Bullers, Samuel J.; Arthur, J. Simon C.; Powrie, Fiona.

In: Cell Host & Microbe, Vol. 22, No. 6, 13.12.2017, p. 733-745.e5.

Research output: Contribution to journalArticle

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

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VL - 22

SP - 733-745.e5

JO - Cell Host & Microbe

JF - Cell Host & Microbe

SN - 1931-3128

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