Abstract
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.
Highlights
We showed in cross-sectional studies that tryptophan (Trp) catabolism into kynurenine (Kyn) by IDO enzyme expressed by dendritic cells (DC) contributes to regulatory T-cells (Tregs) expansion and immune suppression in chronic HIV infection
primary HIV infection (PHI) patients had elevated Kyn/Trp ratio compared to HS and EC and further increased during the chronic phase, while normalized following ART
The frequency of myeloid DC (mDC) and plasmacytoid DC (pDC) decreases over time only for those who remained untreated
Summary
IDO-induced immunosuppressive tryptophan catabolism following primary HIV infection. Mohammad-Ali Jenabian1*, Kishanda Vyboh, Ido Kema, Cynthia Kanagaratham, Danuta Radzioch, Norbert Gilmore, Petronela Ancuta, Cécile Tremblay, Jean-Pierre Routy. From International Symposium HIV and Emerging Infectious Diseases 2014 Marseille, France. From International Symposium HIV and Emerging Infectious Diseases 2014 Marseille, France. 21-23 May 2014
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