Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1306099 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:ACTG A5258, we asked whether chloroquine could reduce the immune activation in HIV infection posited to be driven by microbial TLR agonists, such as bacterial elements translocated from the gut and HIV-1 RNAs . We anticipate that blocking this activation pathway might interfere with events in pathogenesis leading to AIDS- and non-AIDS-related clinical manifestations of HIV disease.
2016-07-15 | GSE71063 | GEO
Project description:ACTG A5258, we asked whether chloroquine could reduce the immune activation in HIV infection posited to be driven by microbial TLR agonists, such as bacterial elements translocated from the gut and HIV-1 RNAs . We anticipate that blocking this activation pathway might interfere with events in pathogenesis leading to AIDS- and non-AIDS-related clinical manifestations of HIV disease.
2016-07-15 | GSE71064 | GEO
Project description:ACTG A5258, we asked whether chloroquine could reduce the immune activation in HIV infection posited to be driven by microbial TLR agonists, such as bacterial elements translocated from the gut and HIV-1 RNAs . We anticipate that blocking this activation pathway might interfere with events in pathogenesis leading to AIDS- and non-AIDS-related clinical manifestations of HIV disease. Blood samples were taken from 20 individuals at week 0 (before treatement) and week 12. 10 individuals received chloroquine 250mg orally and 10 individuals received placebo.
2016-07-15 | E-GEOD-71063 | biostudies-arrayexpress
Project description:ACTG A5258, we asked whether chloroquine could reduce the immune activation in HIV infection posited to be driven by microbial TLR agonists, such as bacterial elements translocated from the gut and HIV-1 RNAs . We anticipate that blocking this activation pathway might interfere with events in pathogenesis leading to AIDS- and non-AIDS-related clinical manifestations of HIV disease. Blood samples were taken from 20 individuals at week 0 (before treatement) and week 12. 10 individuals received chloroquine 250mg orally and 10 individuals received placebo.
2016-07-15 | E-GEOD-71064 | biostudies-arrayexpress
Project description:Macrophages provide an interface between innate and adaptive immunity and are important long-lived reservoirs for Human Immunodeficiency Virus Type-1 (HIV-1). Multiple genetic networks involved in regulating signal transduction cascades and immune responses in macrophages are coordinately modulated by HIV-1 infection. To evaluate complex interrelated processes and to assemble an integrated view of activated signaling networks, a systems biology strategy was applied to genomic and proteomic responses by primary human macrophages over the course of HIV-1 infection. Macrophage responses, including cell cycle, calcium, apoptosis, mitogen-activated protein kinases (MAPK), and cytokines/chemokines, to HIV-1 were temporally regulated, in the absence of cell proliferation. In contrast, Toll-like receptor (TLR) pathways remained unaltered by HIV-1, although TLRs 3, 4, 7, and 8 were expressed and responded to ligand stimulation in macrophages. HIV-1 failed to activate phosphorylation of IRAK-1 or IRF-3, modulate intracellular protein levels of Mx1, an interferon-stimulated gene, or stimulate secretion of TNF, IL-1b, or IL-6. Activation of pathways other than TLR was inadequate to stimulate, via cross-talk mechanisms through molecular hubs, the production of proinflammatory cytokines typical of a TLR response. HIV-1 sensitized macrophage responses to TLR ligands, and the magnitude of viral priming was related to virus replication. HIV-1 induced a primed, proinflammatory state, M1HIV, which increased the responsiveness of macrophages to TLR ligands. HIV-1 might passively evade pattern recognition, actively inhibit or suppress recognition and signaling, or require dynamic interactions between macrophages and other cells, such as lymphocytes or endothelial cells. HIV-1 evasion of TLR recognition and simultaneous priming of macrophages may represent a strategy for viral survival, contribute to immune pathogenesis, and provide important targets for therapeutic approaches. Affymetrix arrays were used to identify genomic macrophage response to HIV during viral spread in culture. Experiment Overall Design: An HIV-1 spreading infection was established in primary human macrophages. RNA was extracted from both viral- and mock-infected macrophages cultures over 7 days and hybridized to Affymetrix HG-U95Av2 GeneChips for analysis.
2009-01-15 | E-GEOD-13395 | biostudies-arrayexpress
Project description:Macrophages provide an interface between innate and adaptive immunity and are important long-lived reservoirs for Human Immunodeficiency Virus Type-1 (HIV-1). Multiple genetic networks involved in regulating signal transduction cascades and immune responses in macrophages are coordinately modulated by HIV-1 infection. To evaluate complex interrelated processes and to assemble an integrated view of activated signaling networks, a systems biology strategy was applied to genomic and proteomic responses by primary human macrophages over the course of HIV-1 infection. Macrophage responses, including cell cycle, calcium, apoptosis, mitogen-activated protein kinases (MAPK), and cytokines/chemokines, to HIV-1 were temporally regulated, in the absence of cell proliferation. In contrast, Toll-like receptor (TLR) pathways remained unaltered by HIV-1, although TLRs 3, 4, 7, and 8 were expressed and responded to ligand stimulation in macrophages. HIV-1 failed to activate phosphorylation of IRAK-1 or IRF-3, modulate intracellular protein levels of Mx1, an interferon-stimulated gene, or stimulate secretion of TNF, IL-1b, or IL-6. Activation of pathways other than TLR was inadequate to stimulate, via cross-talk mechanisms through molecular hubs, the production of proinflammatory cytokines typical of a TLR response. HIV-1 sensitized macrophage responses to TLR ligands, and the magnitude of viral priming was related to virus replication. HIV-1 induced a primed, proinflammatory state, M1HIV, which increased the responsiveness of macrophages to TLR ligands. HIV-1 might passively evade pattern recognition, actively inhibit or suppress recognition and signaling, or require dynamic interactions between macrophages and other cells, such as lymphocytes or endothelial cells. HIV-1 evasion of TLR recognition and simultaneous priming of macrophages may represent a strategy for viral survival, contribute to immune pathogenesis, and provide important targets for therapeutic approaches. Affymetrix arrays were used to identify genomic macrophage response to HIV during viral spread in culture. Keywords: time course
2008-12-15 | GSE13395 | GEO
Project description:Saponin-based vaccine adjuvants are potent in preclinical animal models and humans, but their mechanisms of action remain poorly understood. Using a stabilized HIV envelope trimer as a model immunogen, we carried out studies in non-human primates (NHPs), comparing the most common clinical adjuvant alum and Saponin/MPLA Nanoparticles (SMNP), a novel ISCOMs-like adjuvant. SMNP elicited substantially stronger humoral immune responses than alum and induced strong type I interferon transcriptional signatures, expansion of innate immune cells, and increased antigen presenting cell activation in LNs. These findings indicate that SMNP promotes multiple facets of the early immune response relevant for enhanced immunity to vaccination.
2024-07-01 | GSE264685 | GEO
Project description:The reassorted human 2009 pandemic H1N1 (H1N1pdm) virus infected millions of people and caused thousands of deaths with associated immunopathology. Traditional immunosuppressants have limited capabilities in controlling inflammatory responses associated with severe influenza infections. A new therapeutic strategy, therefore, must be developed. We evaluated several adjuvants including toll-like receptor (TLR) agonists, TLR independent adjuvants and Complete Freund’s adjuvant (CFA) for limiting severe H1N1pdm infection outcomes in a mouse model. In contrast to the TLR agonists and TLR independent adjuvants, CFA which contains multiple pattern recognition receptor (PRR) agonists significantly restrained pro-inflammatory responses and promoted survival in mice from lethal H1N1pdm infection. CFA reduced expression of the plamacytoid dendritic cell (pDC) markers and interferon alpha (IFN-α) after infection, whereas it elevated the T regulatory (Treg) cell suppressive molecules galectin-1 and CTLA-4 expression. Consequently, Th1 cell differentiation and CD8+ effector T cell responses were diminished via downregulated myeloid DC (mDC) costimulation. Furthermore, CTLA-4 expressing Treg cells were dramatically increased when the CFA primed splenocytes were restimulated with its stimuli-killed mycobacterium tuberculosis (M. TB). The elevated CTLA-4 on Treg cells led to reduced CD86 expressing pDCs/mDCs and less CD4+ effector T cells. Overall, our study highlights that the stimuli of innate immunity potentially controls overactive host immune responses in certain situations, and the uncovered mechanism(s) sheds light on the development of anti-influenza therapies. C57B6/J Mice were treated with CFA at day -2 and day 2 post H1N1pdm infection. Weight loss and lethality were monitored post infection. At day 3 and day 5 lung tissues were collected for RNA extraction and expression array analysis.
2014-09-10 | E-GEOD-41088 | biostudies-arrayexpress
Project description:The reassorted human 2009 pandemic H1N1 (H1N1pdm) virus infected millions of people and caused thousands of deaths with associated immunopathology. Traditional immunosuppressants have limited capabilities in controlling inflammatory responses associated with severe influenza infections. A new therapeutic strategy, therefore, must be developed. We evaluated several adjuvants including toll-like receptor (TLR) agonists, TLR independent adjuvants and Complete Freund’s adjuvant (CFA) for limiting severe H1N1pdm infection outcomes in a mouse model. In contrast to the TLR agonists and TLR independent adjuvants, CFA which contains multiple pattern recognition receptor (PRR) agonists significantly restrained pro-inflammatory responses and promoted survival in mice from lethal H1N1pdm infection. CFA reduced expression of the plamacytoid dendritic cell (pDC) markers and interferon alpha (IFN-α) after infection, whereas it elevated the T regulatory (Treg) cell suppressive molecules galectin-1 and CTLA-4 expression. Consequently, Th1 cell differentiation and CD8+ effector T cell responses were diminished via downregulated myeloid DC (mDC) costimulation. Furthermore, CTLA-4 expressing Treg cells were dramatically increased when the CFA primed splenocytes were restimulated with its stimuli-killed mycobacterium tuberculosis (M. TB). The elevated CTLA-4 on Treg cells led to reduced CD86 expressing pDCs/mDCs and less CD4+ effector T cells. Overall, our study highlights that the stimuli of innate immunity potentially controls overactive host immune responses in certain situations, and the uncovered mechanism(s) sheds light on the development of anti-influenza therapies.
2014-09-10 | GSE41088 | GEO