Robust type I interferon (IFN-alpha/beta) production in plasmacytoid dendritic cells (pDCs) is critical for anti-viral immunity. Here we demonstrated a role for the mammalian target of rapamycin (mTOR) pathway in regulating interferon production by pDCs. Inhibition of mTOR or the downstream mediators of mTOR p70S6K1,2 kinases during pDC activation via Toll-like receptor 9 (TLR9) blocked the interaction of TLR9 with the adaptor MyD88 and the subsequent activation of interferon response factor 7 (IRF7), resulting in impaired IFN-alpha production. Microarray analysis confirmed that inhibition of mTOR by the immunosuppressive drug rapamycin suppressed anti-viral and anti-inflammatory gene expression. Consistent with this, targeting rapamycin-encapsulated microparticles to antigen-presenting cells in vivo resulted in a diminution of IFN-alpha production in response to CpG DNA or the yellow fever vaccine virus strain 17D. Thus, mTOR signaling plays a critical role in TLR-mediated IFN-alpha responses by pDCs.
Toll-like receptor-mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTOR-p70S6K pathway.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Systems biology of vaccination for seasonal influenza in humans.
Specimen part, Subject, Time
View SamplesSystems vaccinology has emerged as an interdisciplinary field that combines systems wide measurements and network and predictive modeling applied to vaccinology.
Systems biology of vaccination for seasonal influenza in humans.
Specimen part, Subject, Time
View SamplesSystems vaccinology has emerged as an interdisciplinary field that combines systems wide measurements and network and predictive modeling applied to vaccinology.
Systems biology of vaccination for seasonal influenza in humans.
Specimen part, Subject, Time
View SamplesSystems vaccinology has emerged as an interdisciplinary field that combines systems wide measurements and network and predictive modeling applied to vaccinology.
Systems biology of vaccination for seasonal influenza in humans.
Specimen part, Subject, Time
View SamplesSystems vaccinology has emerged as an interdisciplinary field that combines systems wide measurements and network and predictive modeling applied to vaccinology.
Systems biology of vaccination for seasonal influenza in humans.
Specimen part, Subject, Time
View SamplesMany successful vaccines induce persistent antibody responses that can last a lifetime. The mechanisms by which they do so remain unclear, but emerging evidence suggests that activate dendritic cells (DCs) via Toll-like receptors (TLRs). For example, the yellow fever vaccine YF-17D, one of the most successful empiric vaccines ever developed, activates DCs via multiple TLRs to stimulate pro-inflammatory cytokines. Triggering specific combinations of TLRs in DCs can induce synergistic production of cytokines, which results in enhanced T cell responses, but its impact on antibody responses remain unknown. Learning the critical parameters of innate immunity that programs such antibody responses remains a major challenge in vaccinology. We demonstrated that immunization of mice with synthetic nanoparticles containing antigens plus Toll-like receptor (TLR) ligands 4 (MPL) + 7 (R837) induces synergistic increases in antigen-specific, neutralizing antibodies compared to immunization with a single TLR ligand. To determine whether there was any early programming of B cells, we isolated isotype switched, TCRbeta-CD11b-CD19+IgD-IgG+ B cells by FACS at 7 days post immunization with nanoparticles containing various adjuvants plus OVA, and performed microarray analyses to assess their molecular signatures.
Programming the magnitude and persistence of antibody responses with innate immunity.
Specimen part, Time
View SamplesWe performed systems analyses of immune responses to the meningococcal polysaccharide (MPSV4) and conjugate (MCV4) vaccines in healthy adults.
Molecular signatures of antibody responses derived from a systems biology study of five human vaccines.
Specimen part, Treatment, Time
View SamplesWe compared gene expression profiles between asymptomatic and symptomatic atherosclerotic plaques from the same patient. This was accomplished by analyzing carotid plaques from four patients with bilateral high-grade carotid artery stenoses one being symptomatic (TIA or stroke) and the other asymptomatic.
Microarray analysis reveals overexpression of CD163 and HO-1 in symptomatic carotid plaques.
Sex, Age, Specimen part, Disease, Disease stage, Subject, Time
View SamplesThe aim of the experiment was to compare to single and combined effect of Ikaros activation and IL-7 withdrawal in the Ikaros-null pre-B cell line BH1
Ikaros is absolutely required for pre-B cell differentiation by attenuating IL-7 signals.
Specimen part
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