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

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DOIResolve DOI: http://doi.org/10.1126/science.aaa4921
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TypeArticle
Journal titleScience
ISSN0036-8075
1095-9203
Volume348
Issue6240
Pages12511255
AbstractHost 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 factor 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.
Publication date
LanguageEnglish
AffiliationHuman Health Therapeutics; National Research Council Canada
Peer reviewedYes
NPARC number23000821
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Record identifier74915de0-25bc-4024-9a30-e1fdf4d58c35
Record created2016-10-17
Record modified2016-10-17
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