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J Immunol. 2018 Oct 15;201(8):2385-2391. doi: 10.4049/jimmunol.1801012. Epub 2018 Sep 17.

d-Glycero-β-d-Manno-Heptose 1-Phosphate and d-Glycero-β-d-Manno-Heptose 1,7-Biphosphate Are Both Innate Immune Agonists.

Author information

1
Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and.
2
Vaccine Program, Human Health Therapeutics Research Centre, National Research Council, Ottawa, Ontario K1A 0R6, Canada.
3
Vaccine Program, Human Health Therapeutics Research Centre, National Research Council, Ottawa, Ontario K1A 0R6, Canada Janelle.Sauvageau@nrc-cnrc.gc.ca.

Abstract

d-Glycero-β-d-manno-heptose 1,7-biphosphate (β-HBP) is a novel microbial-associated molecular pattern that triggers inflammation and thus has the potential to act as an immune modulator in many therapeutic contexts. To better understand the structure-activity relationship of this molecule, we chemically synthesized analogs of β-HBP and tested their ability to induce canonical TIFA-dependent inflammation in human embryonic kidney cells (HEK 293T) and colonic epithelial cells (HCT 116). Of the analogs tested, only d-glycero-β-d-manno-heptose 1-phosphate (β-HMP) induced TIFA-dependent NF-κB activation and cytokine production in a manner similar to β-HBP. This finding expands the spectrum of metabolites from the Gram-negative ADP-heptose biosynthesis pathway that can function as innate immune agonists and provides a more readily available agonist of the TIFA-dependent inflammatory pathway that can be easily produced by synthetic methods.

PMID:
30224513
DOI:
10.4049/jimmunol.1801012
[Indexed for MEDLINE]
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