Publication Date:
2015-06-13
Description:
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 kappaB 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gaudet, Ryan G -- Sintsova, Anna -- Buckwalter, Carolyn M -- Leung, Nelly -- Cochrane, Alan -- Li, Jianjun -- Cox, Andrew D -- Moffat, Jason -- Gray-Owen, Scott D -- HOP-13769/Canadian Institutes of Health Research/Canada -- MOP-15499/Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):1251-5. doi: 10.1126/science.aaa4921.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, University of Toronto, Toronto, Canada M5S 1A8. ; Vaccine Program, National Research Council, Ottawa, ON, Canada K1A 0R6. ; 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. ; Department of Molecular Genetics, University of Toronto, Toronto, Canada M5S 1A8. scott.gray.owen@utoronto.ca.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068852" target="_blank"〉PubMed〈/a〉
Keywords:
Adaptor Proteins, Signal Transducing/*immunology/metabolism
;
Burkholderia/immunology
;
Cytosol/chemistry/immunology
;
Escherichia coli/immunology
;
Flagellin/immunology
;
Genetic Testing
;
Gram-Negative Bacteria/*immunology/metabolism
;
HEK293 Cells
;
Host-Pathogen Interactions/genetics/*immunology
;
Humans
;
*Immunity, Innate
;
Jurkat Cells
;
NF-kappa B/immunology
;
Neisseria gonorrhoeae/immunology
;
Neisseria meningitidis/immunology
;
RNA Interference
;
Sugar Phosphates/analysis/*immunology/metabolism
;
TNF Receptor-Associated Factor 6/immunology/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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