Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression data following heptose-bisphosphate (HBP) treatment of Jurkat T cells

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 (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-?B 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. 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

ORGANISM(S): Homo sapiens

SUBMITTER: Scott Gray-Owen

PROVIDER: E-GEOD-67840 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The immune response to Neisseria gonorrhoeae is poorly understood, but its extensive antigenic variability and resistance to complement are thought to allow it to evade destruction by the host’s immune defenses. We propose that N. gonorrhoeae also avoids inducing protective immune responses in the first place. We previously found that N. gonorrhoeae induces IL-17-dependent innate responses in mice and suppresses Th1/Th2-dependent adaptive responses in murine cells in vitro through the induction of TGF-β. In this study using a murine model of vaginal gonococcal infection, mice treated with anti-TGF-β antibody during primary infection showed accelerated clearance of N. gonorrhoeae with incipient development of Th1 and Th2 responses and diminished Th17 responses in genital tract tissue. Upon secondary reinfection, mice that had been treated with anti-TGF-β during primary infection showed anamnestic recall of both Th1 and Th2 responses, with the development of anti-gonococcal antibodies in serum and secretions, and enhanced resistance to reinfection. In knockout mouse strains defective in Th1 or Th2 responses, accelerated clearance of primary infection due to anti-TGF-β treatment was dependent on Th1 but not Th2 activity, whereas resistance to secondary infection resulting from anti-TGF-β treatment during primary infection was due to both Th1- and Th2-dependent memory responses. We propose that N. gonorrhoeae proactively elicits Th-17-driven innate responses that it can resist, and suppresses Th1/Th2-driven specific adaptive immunity that would protect the host. Blockade of TGF-β reverses this pattern of host immune responsiveness and facilitates the emergence of protective anti-gonococcal immunity. We only did microarray assay for wild-type mice with or without anti-TGF-b treatment. Experiment A: Totally there are three groups: Sham-infected mice without treatment; N.gonorrhoeae-infected with control IgG treatment; N.gonorrhoeae-infected with anti-TGF-β treatment. For each group, two mice were studied. Total RNA from mouse vagina were analysed. Experiment B: Totally there are three groups: Sham-reinfected mice without treatment; N.gonorrhoeae-reinfected with control IgG treatment; N.gonorrhoeae-reinfected with anti-TGF-β treatment. For each group, two mice were studied. Total RNA from mouse vagina were analysed.

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Gene expression data following heptose-bisphosphate (HBP) treatment of Jurkat T cells

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