BioProject

Host recognition of pathogen-associated molecular patterns (PAMPs) initiates an innate immune response that is critical for pathogen elimination and engagement of adaptive immunity. More...

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 (LPS) biosynthesis, HBP is highly conserved in Gram-negative bacteria, yet absent from eukaryotic cells. Detection of HBP within the host cytosol activated the NF-κB pathway in vitro, and induced innate and adaptive immune responses in vivo. Moreover, we used a genome-wide RNAi 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. We used a microarray to characterize the gene expression signature induced by HBP. Overall design: We treated two clonal Jurkat T cell lines with culture supernatants prepared from N. gonorrhoeae, a HBP shedding Gram-negative bacteria, or M. catarrhalis, a naturally HBP deficient Gram-negative bacteria. Genes upregulated by N. gonorrhoeae supernatants compared to M. catarrhalis supernatants were considered induced by HBP Less...