2. Academic Validation
  3. INNATE IMMUNITY. Cytosolic detection of the bacterial metabolite HBP activates TIFA-dependent innate immunity

INNATE IMMUNITY. Cytosolic detection of the bacterial metabolite HBP activates TIFA-dependent innate immunity

  • Science. 2015 Jun 12;348(6240):1251-5. doi: 10.1126/science.aaa4921.
Ryan G Gaudet 1,  Anna Sintsova 1,  Carolyn M Buckwalter 1,  Nelly Leung 1,  Alan Cochrane 1,  Jianjun Li 2,  Andrew D Cox 2,  Jason Moffat 3,  Scott D Gray-Owen 4
Affiliations

Affiliations

  • 1 Department of Molecular Genetics, University of Toronto, Toronto, Canada M5S 1A8.
  • 2 Vaccine Program, National Research Council, Ottawa, ON, Canada K1A 0R6.
  • 3 Department of Molecular Genetics, University of Toronto, Toronto, Canada M5S 1A8. Donnelly Centre and Banting and Best Department of Medical Research, University of Toronto, Toronto, Canada M5S 3E1.
  • 4 Department of Molecular Genetics, University of Toronto, Toronto, Canada M5S 1A8. scott.gray.owen@utoronto.ca.
PMID: 26068852 DOI: 10.1126/science.aaa4921
Abstract

Host recognition of pathogen-associated molecular patterns (PAMPs) initiates an innate immune response that is critical for pathogen elimination and engagement of adaptive immunity. Here we show that mammalian cells can detect and respond to the bacterial-derived monosaccharide heptose-1,7-bisphosphate (HBP). A metabolic intermediate in lipopolysaccharide biosynthesis, HBP is highly conserved in Gram-negative bacteria, yet absent from eukaryotic cells. Detection of HBP within the host cytosol activated the nuclear facto κB pathway in vitro and induced innate and adaptive immune responses in vivo. Moreover, we used a genome-wide RNA interference screen to uncover an innate immune signaling axis, mediated by phosphorylation-dependent oligomerization of the TRAF-interacting protein with forkhead-associated domain (TIFA) that is triggered by HBP. Thus, HBP is a PAMP that activates TIFA-dependent immunity to Gram-negative bacteria.

Figures