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Mechanisms of Restoring T Cell Immunity after Cure of Chronic Viral Infection

ABSTRACT: Mechanisms of Restoring T Cell Immunity after Cure of Chronic Viral Infection

PROVIDER: PRJNA749824 | ENA |

REPOSITORIES: ENA

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Mechanisms of Restoring T Cell Immunity after Cure of Chronic Viral Infection

Project description:Mechanisms of Restoring T Cell Immunity after Cure of Chronic Viral Infection

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Mechanisms of Restoring T Cell Immunity after Cure of Chronic Viral Infection

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Mechanisms of Restoring T Cell Immunity after Cure of Chronic Viral Infection

Project description:Understanding the molecular mechanisms of T cell exhaustion and reinvigoration is crucial to improving T cell based immunotherapy. In this study we confirmed key differences between memory and exhausted antigen-specific CD8+ T cells in hepatitis C virus infection before and after antiviral treatment. After viral cure, we observed the although phenotypically they seem to recover, functionally they showed little improvement and critical transcriptional regulators remained in exhausted state.

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Memory-like HCV-specific CD8+ T cells retain a chronic scar after cure of chronic HCV infection

Project description:Investigation of phenotypical changes between exhausted HCV-specific CD8+ T cells during chronic infection and after DAA-mediated cure investigation of heterogeneity withhin the HCV-specific CD8+ T cell population

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Memory-like HCV-specific CD8+ T cells retain a chronic scar after cure of chronic HCV infection

Project description:Chronic hepatitis C virus (HCV) infection is associated with CD8+ T-cell exhaustion characterized by limited effector functions and thus compromised anti-viral activity. Exhausted HCV-specific CD8+ T cells are comprised of memory-like and terminally exhausted CD8+ T-cell subsets. So far, little is not known about the molecular profile and fate of these cells after elimination of chronic antigen stimulation by direct acting antiviral therapy (DAA). Here, we report an antigen-driven molecular core signature underlying exhausted CD8+ T-cell subset heterogeneity in chronic viral infection with a progenitor/progeny relationship of memory-like and terminally exhausted HCV-specific CD8+ T cells via an intermediate stage. Furthermore, transcriptional profiling reveals that the memory-like cells remain after DAA-mediated cure while terminally exhausted HCV-specific CD8+ T-cell subsets are lost. Thus, the memory polarization of the overall HCV-specific CD8+ T-cell response after cure does not result from re-differentiation of exhausted T cells. Consequently, antigen elimination has little impact on the exhausted core signature of memory-like CD8+ T cells that remains clearly different from bona fide T-cell memory. These results identify a molecular signature of T-cell exhaustion that is imprinted like a chronic scar in HCV-specific CD8+ T cells even after HCV cure, highlighting the requirement of re-programming to elicit full effector potential of exhausted T cells.

| EGAS00001004538 | EGA

Memory-like HCV-specific CD8+ T cells retain a molecular scar after cure of chronic HCV infection

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Probiotic consortia improve anti-viral immunity to SARS-CoV-2 in Ferrets [RNA-seq]

Project description:Probiotics have been suggested as one solution to counter detrimental health effects by SARS-CoV-2, however, data so far is scarce. We tested the effect of two probiotic consortia, OL-1 and OL-2, against SARS-CoV2 in ferrets and assessed their effect on cytokine production and transcriptome in a human monocyte- derived macrophage (Mf) and dendritic cell (DC) model. The results showed that the consortia significantly reduced the viral load, modulated immune response, and regulated viral receptor expression in ferrets compared to placebo. In human Mf and DC model, OL-1 and OL-2 induced cytokine production and genes and related to SARS-CoV-2 anti-viral immunity. The study results indicate that probiotic stimulation of the ferret immune system leads to improved anti-viral immunity against SARS-COV-2 and that critical genes and cytokines for anti-SARS-CoV-2 immunity are stimulated in human immune cells in vitro. The effect of the consortia against SARS-CoV-2 warrants further investigations in human clinical trials.

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