Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA226024 | ENA |
REPOSITORIES: ENA
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Project description:This study demonstrates quantitative and qualitative differences between type I IFN signatures in autoimmunity and viral infection using purified CD4pos T cells and CD16pos- and CD16neg-monocyte subsets. We were able to discriminate between cell-specific viral response signatures and the pathogenically amplified IFN signatures observed in autoimmunity. The differences were of both a qualitative and quantitative nature, as the signatures in the patients with SLE were characterized by much more complexly compiled gene patterns with increased absolute gene expression levels.
2014-01-06 | GSE51997 | GEO
Project description:In contrast to pathogenic HIV and SIV infection of humans and macaques, SIV infection of sooty mangabeys (SMs) is typically non-pathogenic despite high virus replication. A key feature of primary SIV infection of SMs is a strong type I interferon (IFN-I) response, characterized by massive up-regulation of interferon-stimulated genes (ISG), followed by rapid resolution during the acute-to-chronic phase transition and establishment of an immune quiescent state that persists throughout the chronic infection. Based on these observations we hypothesized that low levels of IFN-I signaling may be instrumental in preventing chronic immune activation and disease progression in SIV-infected SMs. We used microarrays to characterize gene expression changes induced by IFNalpha treatment. To directly assess the effects of an experimentally-induced augmentation of IFN-I signaling in chronically SIV-infected SMs, we administered recombinant rhesus macaque IFNalpha2-IgFc (rmIFNα2) to eight naturally SIV-infected SMs weekly for 16 weeks and longitudinally monitored viral load, lymphocyte counts, immune activation, SIV-specific CD8+ T-cell responses, and gene expression profile. Administration of rmIFNα2 was bioactive in vivo with gene expression profiling revealing a strong upregulation of numerous ISGs in the blood of treated animals.
2012-07-09 | E-GEOD-35460 | biostudies-arrayexpress
Project description:This ordinary differential equation model is described in the following article:
"Autocrine and paracrine interferon signalling as ‘ring vaccination’ and ‘contact tracing’ strategies to suppress virus infection in a host"
G. Michael Lavigne, Hayley Russell, Barbara Sherry and Ruian Ke
DOI: 10.1098/rspb.2020.3002
Comment:
This model is based on the ordinary differential equations of the non-spatial model of well-mixed viral infection stated in the manuscript (Eq. 2.1 in the article).
Abstract:
The innate immune response, particularly the interferon response, represents a first line of defence against viral infections. The interferon molecules produced from infected cells act through autocrine and paracrine signalling to turn host cells into an antiviral state. Although the molecular mechanisms of IFN signalling have been well characterized, how the interferon response collectively contribute to the regulation of host cells to stop or suppress viral infection during early infection remain unclear. Here, we use mathematical models to delineate the roles of the autocrine and the paracrine signalling, and show that their impacts on viral spread are dependent on how infection proceeds. In particular, we found that when infection is well-mixed, the paracrine signalling is not as effective; by contrast, when infection spreads in a spatial manner, a likely scenario during initial infection in tissue, the paracrine signalling can impede the spread of infection by decreasing the number of susceptible cells close to the site of infection. Furthermore, we argue that the interferon response can be seen as a parallel to population-level epidemic prevention strategies such as ‘contact tracing’ or ‘ring vaccination’. Thus, our results here may have implications for the outbreak control at the population scale more broadly.
2021-08-11 | BIOMD0000001021 | BioModels
Project description:Type I interferons are critical anti-viral cytokines during virus infections and have also been implicated in the pathogenesis of systemic lupus erythematosus (SLE). The secretion of type I interferon of pDCs is modulated by Siglec-H, a DAP12 associated receptor on pDCs. We showed that Siglec-H deficient pDCs produce more of the type I interferon IFN-α in vitro and that Siglec-H ko mice produce more IFN-α after murine cytomegalovirus (mCMV) infection in vivo, leading to efficient clearance of the virus. Furthermore, ageing Siglec-H ko mice showed a mild form of systemic autoimmunity. In contrast, Siglec-H ko mice developed a severe form of systemic lupus-like autoimmune disease with strong kidney nephritis several weeks after a single mCMV infection. This induction of systemic autoimmune disease after virus infection in Siglec-H ko mice was accompanied by a type I interferon signature and fully dependent on type I interferon signaling. These results show that Siglec-H normally serves as modulator of type I interferon responses after infection with a persistent virus and thereby prevents induction of autoimmune disease. For microarray experiments gene expression profiles of total splenic cells from two wt and Siglec-H ko mice 26 weeks after infection with luciferase expressing murine Cytomegalovirus (5x105 pfu) or from two uninfected wt and Siglec-H ko control mice were analyzed
2016-03-16 | E-GEOD-79248 | biostudies-arrayexpress
Project description:Impaired type I interferon (IFN) responses are predictive of severe disease during pulmonary coronavirus infection. Insufficient IFN-responsiveness is associated with viremia and hypercytokinemia, however the resolution of IFN-dependent innate immune responses in the lungs remains limited. Here, we aimed to elucidate the early dynamics of antiviral immunity and define the IFN-dependent mechanisms limiting viral spread during pulmonary infection with the murine coronavirus A59 (M-CoV-A59), a beta-coronavirus. Combining high-resolution transcriptomic analysis and genetic attenuation of interferon signaling, we delineated IFN-dependent cell-intrinsic and population-based transcriptional changes that determined viral replication and inflammatory maturation, respectively.
2023-01-02 | E-MTAB-11781 | biostudies-arrayexpress
Project description:The antiviral immune response to SARS-CoV-2 infection can limit viral spread and prevent development of pneumonic COVID-19. However, the protective immunological response associated with successful viral containment in the upper airways remain unclear. Here, we combine a multiomics approach with longitudinal sampling to reveal temporally resolved protective immune signatures in non-pneumonic and ambulatory SARS-CoV-2 infected patients and associate specific immune trajectories with upper airway viral containment. We see a distinct systemic rather than local immune state associated with viral containment, characterized by interferon stimulated gene (ISG) upregulation across circulating immune cell subsets in non-pneumonic SARS-CoV2 infection. We report reduced cytotoxic potential of Natural Killer (NK) and T cells, and an immune-modulatory monocyte phenotype with protective immunity in COVID-19. Together, we show protective immune trajectories in SARS-CoV2 infection, which have important implications for patient prognosis and the development of immunomodulatory therapies.
2022-01-17 | PXD030785 | Pride
Project description:Upon antigenic stimulation, naïve CD4+ T cells differentiate into phenotypically distinct T helper cells. Naïve T cells are considered homogenous save for their unique T cell receptor (TCR), thought to confer distinct differentiation potential according to its affinity for cognate antigen. Here we show that naïve T cells are transcriptionally heterogeneous and identify a role for type I interferon (IFN) in shaping this heterogeneity. Using complementary single cell analyses, we show that T cell fate is independent of TCR and identify a role for type I IFN signaling in regulating the early differentiation of naïve CD4 T cells towards central memory precursors. Thus, naïve CD4 T cell differentiation potential is determined by environmental cues both prior to and during priming. IFN-conditioned naïve CD4 T cells are expanded in human viral infection and autoimmunity highlighting the relevance of this pathway to beneficial and maladaptive T cell responses, as well as its therapeutic potential for enhanced T cell memory formation.
2023-03-22 | GSE171527 | GEO
Project description:While inhibition of T cell co-inhibitory receptors has revolutionized cancer therapy, the mechanisms governing their expression on human T cells have not been elucidated. Type 1 interferon (IFN-I) modulates T cell immunity in viral infection, autoimmunity, and cancer, and may facilitate induction of T cell exhaustion in chronic viral infection. Here we show that IFN-I regulates co-inhibitory receptor expression on human T cells, inducing PD-1/TIM-3/LAG-3 while surprisingly inhibiting TIGIT expression. High-temporal-resolution mRNA profiling of IFN-I responses enabled the construction of dynamic transcriptional regulatory networks uncovering three temporal transcriptional waves. Perturbation of key transcription factors on human primary T cells revealed unique regulators that control expression of co-inhibitory receptors. We found that the dynamic IFN-I response in vitro closely mirrored T cell features with IFN-I linked acute SARS-CoV-2 infection in human, with high LAG3 and decreased TIGIT expression. Finally, our gene regulatory network identified SP140 as a key regulator for differential LAG3 and TIGIT expression, which were validated at the level of protein expression. The construction of IFN-I regulatory networks with identification of unique transcription factors controlling co-inhibitory receptor expression may provide targets for enhancement of immunotherapy in cancer, infectious diseases, and autoimmunity.
2022-01-31 | GSE195541 | GEO
Project description:While inhibition of T cell co-inhibitory receptors has revolutionized cancer therapy, the mechanisms governing their expression on human T cells have not been elucidated. Type 1 interferon (IFN-I) modulates T cell immunity in viral infection, autoimmunity, and cancer, and may facilitate induction of T cell exhaustion in chronic viral infection. Here we show that IFN-I regulates co-inhibitory receptor expression on human T cells, inducing PD-1/TIM-3/LAG-3 while surprisingly inhibiting TIGIT expression. High-temporal-resolution mRNA profiling of IFN-I responses enabled the construction of dynamic transcriptional regulatory networks uncovering three temporal transcriptional waves. Perturbation of key transcription factors on human primary T cells revealed unique regulators that control expression of co-inhibitory receptors. We found that the dynamic IFN-I response in vitro closely mirrored T cell features with IFN-I linked acute SARS-CoV-2 infection in human, with high LAG3 and decreased TIGIT expression. Finally, our gene regulatory network identified SP140 as a key regulator for differential LAG3 and TIGIT expression, which were validated at the level of protein expression. The construction of IFN-I regulatory networks with identification of unique transcription factors controlling co-inhibitory receptor expression may provide targets for enhancement of immunotherapy in cancer, infectious diseases, and autoimmunity.
2022-01-31 | GSE195540 | GEO
Project description:While inhibition of T cell co-inhibitory receptors has revolutionized cancer therapy, the mechanisms governing their expression on human T cells have not been elucidated. Type 1 interferon (IFN-I) modulates T cell immunity in viral infection, autoimmunity, and cancer, and may facilitate induction of T cell exhaustion in chronic viral infection. Here we show that IFN-I regulates co-inhibitory receptor expression on human T cells, inducing PD-1/TIM-3/LAG-3 while surprisingly inhibiting TIGIT expression. High-temporal-resolution mRNA profiling of IFN-I responses enabled the construction of dynamic transcriptional regulatory networks uncovering three temporal transcriptional waves. Perturbation of key transcription factors on human primary T cells revealed unique regulators that control expression of co-inhibitory receptors. We found that the dynamic IFN-I response in vitro closely mirrored T cell features with IFN-I linked acute SARS-CoV-2 infection in human, with high LAG3 and decreased TIGIT expression. Finally, our gene regulatory network identified SP140 as a key regulator for differential LAG3 and TIGIT expression, which were validated at the level of protein expression. The construction of IFN-I regulatory networks with identification of unique transcription factors controlling co-inhibitory receptor expression may provide targets for enhancement of immunotherapy in cancer, infectious diseases, and autoimmunity.
2022-01-31 | GSE195542 | GEO