IDO-induced immunosuppressive tryptophan catabolism following primary HIV infection
نویسندگان
چکیده
Methods Plasma and Peripheral blood mononuclear cells (PBMCs) were longitudinally collected in 41 PHI patients (infection <90 days), 24 remained untreated (ART-naive) and 17 were ART-treated one year later. In addition, samples from elite controllers (EC, n=12) and healthy subjects (HS, n=12) were also assessed. IDO enzymatic activity marker (Kyn/Trp ratio) was measured by isotope dilution tandem mass spectrometry. IL-6, IL-18, TNF-a and IP-10 plasma levels were assessed by Luminex. Frequency of Tregs (CD4+CD25highCD127lowFOXP3high), CD11c+ myeloid DC (mDC) and CD123+ plasmacytoid DC (pDC) as well as HLA-DR/CD38 co-expression of on T-cells were assessed.
منابع مشابه
Liver fibrosis is strongly associated with an enhanced level of immunosuppressive tryptophan catabolism independently of HCV viremia in ART-treated HIV/HCV co-infected patients
Background HCV infection induces hepatic and extra-hepatic damage that includes kidney and neurocognitive dysfunction. Tryptophan (Trp) is catabolized into immunosuppressive kynurenine (Kyn) by indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3 dioxegenase (TDO). Increased Trp catabolism measured by Kyn/Trp ratio has been associated with neurocognitive impairment and immune dysfunction in HIV...
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Tryptophan (Trp) catabolism into immunosuppressive kynurenine (Kyn) by indoleamine 2,3-dioxygenase (IDO) was previously linked to Th17/Treg differentiation and immune activation. Here we examined Trp catabolism and its impact on Th17/Treg balance in uninfected healthy subjects (HS) and a large cohort of HIV-infected patients with different clinical outcomes: ART-naïve, Successfully Treated (ST)...
متن کاملHIV inhibits CD4+ T-cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells.
Infection with the human immunodeficiency virus type-1 (HIV) results in acute and progressive numeric loss of CD4(+) T-helper cells and functional impairment of T-cell responses. The mechanistic basis of the functional impairment of the surviving cells is not clear. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme that inhibits T-cell proliferation by catabolizing the essential ...
متن کاملHuman bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation.
Marrow stromal cells (MSCs) inhibit allogeneic T-cell responses, yet the molecular mechanism mediating this immunosuppressive effect of MSCs remains controversial. Recently, expression of indoleamine 2,3-dioxygenase (IDO), which is induced by interferon-gamma (IFN-gamma) and catalyzes the conversion from tryptophan to kynurenine, has been identified as a T-cell inhibitory effector pathway in pr...
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BACKGROUND Tryptophan (Trp) catabolism into kynurenine (Kyn) contributes to immune dysfunction in chronic human immunodeficiency virus (HIV) infection. To better define the relationship between Trp catabolism, inflammation, gut mucosal dysfunction, and the role of early antiretroviral therapy (ART), we prospectively assessed patients early after they acquired HIV. METHODS Forty patients in th...
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