An intestinal commensal symbiosis factor controls neuroinflammation via TLR2-mediated CD39 signalling

Yan Wang, Kiel M. Telesford, Javier Ochoa-Repáraz, Sakhina Haque-Begum, Marc Christy, Eli J. Kasper, Li Wang, Yan Wu, Simon C. Robson, Dennis L. Kasper and Lloyd H. Kasper ()
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Yan Wang: Geisel School of Medicine, Dartmouth College
Kiel M. Telesford: Geisel School of Medicine, Dartmouth College
Javier Ochoa-Repáraz: Geisel School of Medicine, Dartmouth College
Sakhina Haque-Begum: Geisel School of Medicine, Dartmouth College
Marc Christy: Geisel School of Medicine, Dartmouth College
Eli J. Kasper: Geisel School of Medicine, Dartmouth College
Li Wang: Medical College of Wisconsin
Yan Wu: Beth Israel Deaconess Medical Center, Harvard Medical School
Simon C. Robson: Beth Israel Deaconess Medical Center, Harvard Medical School
Dennis L. Kasper: Harvard Medical School
Lloyd H. Kasper: Geisel School of Medicine, Dartmouth College

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: Abstract The mammalian immune system constitutively senses vast quantities of commensal bacteria and their products through pattern recognition receptors, yet excessive immune reactivity is prevented under homeostasis. The intestinal microbiome can influence host susceptibility to extra-intestinal autoimmune disorders. Here we report that polysaccharide A (PSA), a symbiosis factor for the human intestinal commensal Bacteroides fragilis, protects against central nervous system demyelination and inflammation during experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, through Toll-like receptor 2 (TLR2). TLR2 mediates tissue-specific expansion of a critical regulatory CD39+ CD4 T-cell subset by PSA. Ablation of CD39 signalling abrogates PSA control of EAE manifestations and inflammatory cytokine responses. Further, CD39 confers immune-regulatory phenotypes to total CD4 T cells and Foxp3+ CD4 Tregs. Importantly, CD39-deficient CD4 T cells show an enhanced capability to drive EAE progression. Our results demonstrate the therapeutic potential and underlying mechanism by which an intestinal symbiont product modulates CNS-targeted demyelination.

Date: 2014
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DOI: 10.1038/ncomms5432

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