Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA285919 | ENA |
REPOSITORIES: ENA
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Project description:BACKGROUND: Patients with HIV that are coinfected with HCV are at increased risk for rapidly progressive liver disease and subsequently the development of Hepatocellular Carcinoma (HCC). Specifically, HCC develops earlier in coinfected patients and these patients are more symptomatic than those with only HCV infection at diagnosis suggesting that both viruses increase the propensity for malignant transformation. Consequently, HCV coinfection and the associated liver disease is a major health burden for HIV infected persons in the U.S. However, the genetic and cellular based mechanisms underpinning how HCV initiates and subsequently induces liver pathology and why coinfection with HIV results in significantly worse hepatic disease remains to be clarified. In addition, the specific cell types that contribute to these clinical outcomes are unknown. METHODS: The goal of this project is focused on understanding the molecular mechanisms underlying the hepatic sequela in coinfected patients specifically focusing on the innate inflammatory responses activated by HIV in liver cells. To this end, we have developed novel in-vitro models that utilize HIV stimulated primary kupffer cells (PKCs). RESULTS: HIV stimulation of primary kupffer cells resulted in rapid and robust upregulation of an inflammatory gene signature. The goal of this study is to characterize the changes in gene expression triggered by HIV in primary human kupffer cells.
2018-10-26 | GSE69589 | GEO
Project description:Kupffer cells are the first line of defense in the liver against pathogens, yet several microbes successfully target the liver, bypass immune surveillance, and effectively develop in this tissue. Our current, albeit poor, understanding of Kupffer cell-pathogen interactions has been largely achieved through the study of primary cells, requiring isolation from a large numbers of animals. To facilitate the study of Kupffer cell biology, an immortalized rat Kupffer cell line, RKC1, was developed. We performed a comparative global proteomic analysis of RKC1 and primary rat Kupffer cells (PRKC) to characterize their respective responses to lipopolysaccharide (LPS)-mediated immune stimulation. We identified patent differences in the proteomic response profile of RKC1 and PRKC to LPS. We observed that PRKC upregulated more immune function pathways and exhibited marked changes in cellular morphology following stimulation. We consequently analyzed the cytoskeletal signaling pathways of these cells in light of the fact that macrophages are known to induce cytoskeletal changes in response to pathogens. Our findings suggest that Kupffer cells respond differently to inflammatory stimulus than do monocyte-derived macrophages, and such data may provide insight into how pathogens, such as the malaria parasite, may have evolved mechanisms of liver entry through Kupffer cells without detection.
2016-07-22 | MSV000079995 | MassIVE
Project description:HBV Infection and DNA Stimulation Induce a Unique Innate Immune Response in Hepatocytes
| PRJNA285918 | ENA
Project description:Kupffer cells are the first line of defense in the liver against pathogens, yet several microbes successfully target the liver, bypass immune surveillance, and effectively develop in this tissue. Our current, albeit poor, understanding of Kupffer cell-pathogen interactions has been largely achieved through the study of primary cells, requiring isolation from a large numbers of animals. To facilitate the study of Kupffer cell biology, an immortalized rat Kupffer cell line, RKC1, was developed. We performed a comparative global proteomic analysis of RKC1 and primary rat Kupffer cells (PRKC) to characterize their respective responses to lipopolysaccharide (LPS)-mediated immune stimulation. We identified patent differences in the proteomic response profile of RKC1 and PRKC to LPS. We observed that PRKC upregulated more immune function pathways and exhibited marked changes in cellular morphology following stimulation. We consequently analyzed the cytoskeletal signaling pathways of these cells in light of the fact that macrophages are known to induce cytoskeletal changes in response to pathogens. Our findings suggest that Kupffer cells respond differently to inflammatory stimulus than do monocyte-derived macrophages, and such data may provide insight into how pathogens, such as the malaria parasite, may have evolved mechanisms of liver entry through Kupffer cells without detection.
2015-07-03 | PXD001247 | Pride
Project description:Dendritic cells (DC) serve a key function in host defense, linking innate detection of microbes to the activation of pathogen-specific adaptive immune responses. Whether there is cell-intrinsic recognition of HIV-1 by host innate pattern-recognition receptors and subsequent coupling to antiviral T cell responses is not yet known. DC are largely resistant to infection with HIV-1, but facilitate infection of co-cultured T-helper cells through a process of trans-enhancement. We show here that, when DC resistance to infection is circumvented, HIV-1 induces DC maturation, an antiviral type I interferon response and activation of T cells. This innate response is dependent on the interaction of newly-synthesized HIV-1 capsid (CA) with cellular cyclophilin A (CypA) and the subsequent activation of the transcription factor IRF3. Because the peptidyl-prolyl isomerase CypA also interacts with CA to promote HIV-1 infectivity, our results suggest that CA conformation has evolved under opposing selective pressures for infectivity versus furtiveness. Thus, a cell intrinsic sensor for HIV-1 exists in DC and mediates an antiviral immune response, but it is not typically engaged due to absence of DC infection. The virulence of HIV-1 may be related to evasion of this response, whose manipulation may be necessary to generate an effective HIV-1 vaccine. We analyzed the gene expression profiles of uninfected human monocyte-derived dendritic cells (MDDCs) and MDDCs infected with an envelope-defective GFP-encoding VSV-G-pseudotyped HIV-1 vector (HIVGFP(G)) and with VSV-G pseudotyped virus-like particles derived from SIVmac to deliver Vpx (SIVVLP(G)), alone or in combination. Cells were infected at day 4 of differentiation and cells were harvested 48 hours later. RNA was extracted with TRIzol. RNA was labeled and hybridized to Human Genome U133A 2.0 arrays arrays following the Affymetrix protocols. Data were analyzed in R and Bioconductor.
2010-09-09 | E-GEOD-22589 | biostudies-arrayexpress
Project description:Mycobacterial infection induces a specific human innate immune response
| PRJNA279959 | ENA
Project description:Aguilera 2014 - HIV latency. Interaction
between HIV proteins and immune response
This model is described in the article:
Studying HIV latency by
modeling the interaction between HIV proteins and the innate
immune response.
Aguilera LU,
Rodríguez-González J.
J. Theor. Biol. 2014 Nov; 360:
67-77
Abstract:
HIV infection leads to two cell fates, the viral productive
state or viral latency (a reversible non-productive state). HIV
latency is relevant because infected active CD4+ T-lymphocytes
can reach a resting memory state in which the provirus remains
silent for long periods of time. Despite experimental and
theoretical efforts, the causal molecular mechanisms
responsible for HIV latency are only partially understood.
Studies have determined that HIV latency is influenced by the
innate immune response carried out by cell restriction factors
that inhibit the postintegration steps in the virus replication
cycle. In this study, we present a mathematical study that
combines deterministic and stochastic approaches to analyze the
interactions between HIV proteins and the innate immune
response. Using wide ranges of parameter values, we observed
the following: (1) a phenomenological description of the viral
productive and latent cell phenotypes is obtained by bistable
and bimodal dynamics, (2) biochemical noise reduces the
probability that an infected cell adopts the latent state, (3)
the effects of the innate immune response enhance the HIV
latency state, (4) the conditions of the cell before infection
affect the latent phenotype, i.e., the existing expression of
cell restriction factors propitiates HIV latency, and existing
expression of HIV proteins reduces HIV latency.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000573.
To cite BioModels Database, please use:
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To the extent possible under law, all copyright and related or
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2024-09-02 | BIOMD0000000573 | BioModels
Project description:This SuperSeries is composed of the following subset Series: GSE22768: Systems analysis of the Merck Ad5/HIV vaccine reveals robust induction of a core innate immune gene network: in vivo analysis GSE22769: Systems analysis of the Merck Ad5/HIV vaccine reveals robust induction of a core innate immune gene network: in vitro analysis To better understand how innate immune responses to vaccination can lead to lasting protective immunity, we used a systems approach to define immune signatures in humans over 1 wk following MRKAd5/HIV vaccination that predicted subsequent HIV-specific T-cell responses. Within 24 h, striking increases in peripheral blood mononuclear cell gene expression associated with inflammation, IFN response, and myeloid cell trafficking occurred, and lymphocyte-specific transcripts decreased. These alterations were corroborated by marked serum inflammatory cytokine elevations and egress of circulating lymphocytes. Responses of vaccinees with preexisting adenovirus serotype 5 (Ad5) neutralizing antibodies were strongly attenuated, suggesting that enhanced HIV acquisition in Ad5-seropositive subgroups in the Step Study may relate to the lack of appropriate innate activation rather than to increased systemic immune activation. Importantly, patterns of chemoattractant cytokine responses at 24 h and alterations in 209 peripheral blood mononuclear cell transcripts at 72 h were predictive of subsequent induction and magnitude of HIV-specific CD8(+) T-cell responses. This systems approach provides a framework to compare innate responses induced by vectors, as shown here by contrasting the more rapid, robust response to MRKAd5/HIV with that to yellow fever vaccine. When applied iteratively, the findings may permit selection of HIV vaccine candidates eliciting innate immune response profiles more likely to drive HIV protective immunity. Refer to individual Series
2012-11-20 | E-GEOD-22822 | biostudies-arrayexpress
Project description:Dendritic cells (DC) serve a key function in host defense, linking innate detection of microbes to the activation of pathogen-specific adaptive immune responses. Whether there is cell-intrinsic recognition of HIV-1 by host innate pattern-recognition receptors and subsequent coupling to antiviral T cell responses is not yet known. DC are largely resistant to infection with HIV-1, but facilitate infection of co-cultured T-helper cells through a process of trans-enhancement. We show here that, when DC resistance to infection is circumvented, HIV-1 induces DC maturation, an antiviral type I interferon response and activation of T cells. This innate response is dependent on the interaction of newly-synthesized HIV-1 capsid (CA) with cellular cyclophilin A (CypA) and the subsequent activation of the transcription factor IRF3. Because the peptidyl-prolyl isomerase CypA also interacts with CA to promote HIV-1 infectivity, our results suggest that CA conformation has evolved under opposing selective pressures for infectivity versus furtiveness. Thus, a cell intrinsic sensor for HIV-1 exists in DC and mediates an antiviral immune response, but it is not typically engaged due to absence of DC infection. The virulence of HIV-1 may be related to evasion of this response, whose manipulation may be necessary to generate an effective HIV-1 vaccine.
2010-09-09 | GSE22589 | GEO
Project description:Virulent Francisella tularensis induces a unique pulmonary inflammatory response characterized by temporal regulation of innate immune pathways correlating with altered bacterial gene expression patterns. The pulmonary transcriptional response to aerosolized virulent F. tularensis was compared to other lethal and non-lethal respiratory pathogens.
2013-04-15 | E-GEOD-44320 | biostudies-arrayexpress