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

被引：91

作者：

Danne, Camille ^{[1
]}

Ryzhakov, Grigory ^{[1
]}

Martinez-Lopez, Maria ^{[2
]}

Ilott, Nicholas Edward ^{[1
]}

Franchini, Fanny ^{[1
]}

Cuskin, Fiona ^{[3
]}

Lowe, Elisabeth C. ^{[3
]}

Bullers, Samuel J. ^{[1
]}

Arthur, J. Simon C. ^{[4
]}

Powrie, Fiona ^{[1
]}

机构：

[1] Univ Oxford, Kennedy Inst Rheumatol, Oxford, England

[2] Fdn Ctr Nacl Invest Cardiovasc Carlos III CNIC, Immunobiol Lab, Melchor Fernandez Almagro 3, Madrid, Spain

[3] Newcastle Univ, Med Sch, Inst Cell & Mol Biosci, Newcastle Upon Tyne, Tyne & Wear, England

[4] Univ Dundee, Div Cell Signaling & Immunol, Sch Life Sci, Dundee, Scotland

来源：

CELL HOST & MICROBE | 2017年 / 22卷 / 06期

基金：

英国惠康基金;

关键词：

INFLAMMATORY-BOWEL-DISEASE; NEGATIVE REGULATORS; KINASES MSK1; RECEPTOR; INTERLEUKIN-10; CELLS; INNATE; POLARIZATION; ACTIVATION; COMMENSAL;

D O I：

10.1016/j.chom.2017.11.002

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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 antiinflammatory 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.

引用

页码：733 / +

页数：18

共 61 条

[1] The kinases MSK1 and MSK2 act as negative regulators of Toll-like receptor signaling [J].