Transcriptional profiles of Ad-F7 transduced macrophages treated with anti-IFNAR2 antibody or control isotype (IgG)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE12002 | GEO | 2008/11/30
SECONDARY ACCESSION(S): PRJNA114297
REPOSITORIES: GEO
Similar Datasets
Project description:Determine the role of interferons in the transcriptional profile of Ad-F7 transduced primary human macrophages using neutralizing antibody for the type I IFN receptor (IFNAR2). Primary human macrophage preparations were transduced with Ad-GFP or Ad-F7 and treated with control isotype (IgG) or neutralizing antibody for the type I IFN receptor (IFNAR2). RNA was collected 24 hours later and subjected to microarray analysis. Data represents the average of 5 donors.
2008-11-29 | E-GEOD-12002 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE11926: Transcriptional profiles of Ad-F3 and Ad-F7 transduced macrophages. GSE12002: Transcriptional profiles of Ad-F7 transduced macrophages in the presence of neutralizing antibody for the type I interferon receptor (IFNAR2) or control isotype (IgG). Refer to individual Series
2008-11-29 | E-GEOD-12120 | biostudies-arrayexpress
Project description:To identify genes that may regulate distinct or overlapping functions of IRF-3 and IRF-7, primary human macrophage preparations were transduced with adenoviral vectors: Ad-GFP (control), Ad-F3 (expressing the active form of IRF-3, IRF-3 5D), or Ad-F7 (expressing the active form of IRF-7, IRF-7 D247-467) and evaluated by microarray analysis. RNA was collected 24 hours post-transduction with Ad-GFP, Ad-F3 and Ad-F7 and subjected to microarray analysis. Submited tables show the average of 7 donors.
2008-11-29 | E-GEOD-11926 | biostudies-arrayexpress
Project description:To identify genes that may regulate distinct or overlapping functions of IRF-3 and IRF-7, primary human macrophage preparations were transduced with adenoviral vectors: Ad-GFP (control), Ad-F3 (expressing the active form of IRF-3, IRF-3 5D), or Ad-F7 (expressing the active form of IRF-7, IRF-7 D247-467) and evaluated by microarray analysis.
2008-11-30 | GSE11926 | GEO
Project description:Transcriptional profiles of Ad-F7 transduced macrophages treated with anti-IFNAR2 antibody or control isotype (IgG)
| PRJNA114297 | ENA
Project description:HIV-1 infection occurs primarily through mucosal transmission. Application of biologically relevant mucosal models can advance understanding of the functional properties of antibodies that mediate HIV protection, thereby guiding antibody-based vaccine development. Here, we employed a human ex vivo vaginal HIV-1 infection model and a rhesus macaque in vivo intrarectal SHIV challenge model to probe the protective capacity of monoclonal broadly-neutralizing (bnAb) and non-neutralizing Abs (nnAbs) that were functionally modified by isotype switching. For human vaginal explants, we developed a replication-competent, secreted NanoLuc reporter virus system and showed that CD4 binding site bnAbs b12 IgG1 and CH31 IgG1 and IgA2 isoforms potently blocked HIV-1JR-CSF and HIV-1Bal26 infection. However, IgG1 and IgA nnAbs, either alone or together, did not inhibit infection despite the presence of FcR-expressing effector cells in the tissue. In macaques, the CH31 IgG1 and IgA2 isoforms infused before high-dose SHIV challenge were completely to partially protective, respectively, while nnAbs (CH54 IgG1 and CH38 mIgA2) were non-protective. Importantly, in both mucosal models IgG1 isotype bnAbs were more protective than the IgA2 isotypes, attributable in part to greater neutralization activity of the IgG1 variants. These findings underscore the importance of potent bnAb induction as a primary goal of HIV-1 vaccine development.
| S-EPMC5161443 | biostudies-literature
Project description:Type I interferons (IFNs) are a family of cytokines that play an important role in regulating immune responses to pathogens and tumors and are used therapeutically. All IFNs are considered to signal via the heterodimeric IFNAR1-IFNAR2 complex, yet some subtypes such as IFN? can exhibit distinct functional properties, although the molecular basis of this is unclear. Here we demonstrate IFN uniquely and specifically ligates to IFNAR1 in an IFNAR2-independent manner and provide the structural basis of the IFNAR1-IFN interaction. We show that the IFNAR1-IFN complex transduces signals to modulate the expression of a set of genes independently of IFNAR2. Moreover, we show the in vivo importance of the IFNAR1-IFN signaling axis in a murine model of LPS-induced septic shock. Thus, we provide a molecular basis for understanding specific functions of IFN?. Interferon b induced gene expression in peritoneal exudate cells was measured 3hr post intra-peritoneal injection of 10,000IU/ml of interferon beta or saline into wildtype and Ifnar2-/- mice. Three independant experiments were performed for each treatment in both genotypes using different mice for each sample.
2013-07-13 | E-GEOD-48827 | biostudies-arrayexpress
Project description:Approximately 100,000 mother-to-child transmission (MTCT) events of HIV via human milk feeding occur each year. However, only about 15% of infants milk-fed by untreated HIV+ mothers become infected, suggesting a protective effect of the milk itself. Infants ingest 105-108 maternal leukocytes daily via milk, which remain functional beyond ingestion. Such function may be elicited by maternal milk antibody (Ab). Though IgA is dominant in milk, most HIV-specific milk Abs are of the IgG subclass, highlighting the importance of investigating the function of each IgG isotype in the milk context. Though Ab effector function mediated by the constant (Fc) domain via interaction with Fc Receptors (FcRs), such as Ab-dependent cellular phagocytosis (ADCP), are critical in protecting against HIV infection, ADCP is largely unexplored as it relates to mitigation of MTCT. Presently we report the ADCP activity of milk leukocytes against HIV particles and immune complexes (ICs), using 57 unique samples from 34 women, elicited by IgG1/2/3/4 of monoclonal (m)Ab 246-D. Granulocyte ADCP of HIV was most potent compared to other phagocytes when elicited by IgG1/3/4. IgG1/3 activated granulocytes similarly, exhibiting 1.6x-4.4x greater activity compared to IgG2/4, and a preference for virus compared to ICs. Notably, CD16- monocyte ADCP of a given target were unaffected by isotype, and CD16+ monocytes were poorly stimulated by IgG1. IgG2/4 elicited potent IC ADCP, and in terms of total leukocyte IC ADCP, IgG4 and IgG3 exhibited similar function, with IgG4 eliciting 1.6x-2.1x greater activity compared to IgG1/IgG2, and CD16+ monocytes most stimulated by IgG2. These data contribute to a more comprehensive understanding of Fc-mediated functionality of milk leukocytes, which is critical in order to develop therapeutic approaches to eliminating this route of MTCT, including mucosal administration of mAbs and/or a maternal vaccination aimed to elicit a potent milk Ab response.
| S-EPMC9110811 | biostudies-literature
Project description:Identifying the mechanisms of natural control of HIV-1 infection could lead to novel approaches to prevent or cure HIV infection. Several studies have associated natural control of HIV-1 infection with IgG Abs against HIV-1 Gag proteins (e.g., p24) and/or production of IgG2 Abs against HIV-1 proteins. These Abs likely exert their effect by activating antiviral effector cell responses rather than virus neutralization. We hypothesized that an opsonophagocytic IgG Ab response against HIV-1 p24 that activates plasmacytoid dendritic cells (pDCs) through Fc?RIIa would be associated with control of HIV and that this would be enhanced by Ab isotype diversification. Using the Gen2.2 pDC cell line, we demonstrated that pDC-reactive opsonophagocytic IgG Ab responses against HIV-1 p24 were higher in HIV controllers (HIV RNA < 2000 copies/ml) than noncontrollers (HIV RNA > 10,000 copies/ml), particularly in controllers with low but detectable viremia (HIV RNA 75-2000 copies/ml). Opsonophagocytic Ab responses correlated with plasma levels of IgG1 and IgG2 anti-HIV-1 p24 and, notably, correlated inversely with plasma HIV RNA levels in viremic HIV patients. Phagocytosis of these Abs was mediated via Fc?RIIa. Isotype diversification (toward IgG2) was greatest in HIV controllers, and depletion of IgG2 from Ig preparations indicated that IgG2 Abs to HIV-1 p24 do not enhance phagocytosis, suggesting that they enhance other aspects of Ab function, such as Ag opsonization. Our findings emulate those for pDC-reactive opsonophagocytic Ab responses against coxsackie, picorna, and influenza viruses and demonstrate a previously undefined immune correlate of HIV-1 control that may be relevant to HIV vaccine development.
| S-EPMC4492937 | biostudies-literature
Project description:Schistosoma mansoni - virus transduced
| PRJEB1286 | ENA