INVESTIGADORES
OSTROWSKI Matias
congresos y reuniones científicas
Título:
Extracellular vesicles released by HIV-infected CD4+ T cells promote the secretion of proinflammatory cytokines by uninfected bystander lymphocytes: Role of Hypoxia inducible factor 1 alpha.
Autor/es:
MATIAS OSTROWSKI; DUETTE, GABRIEL
Lugar:
Toronto
Reunión:
Congreso; Reunión Anual de la "International Society for Extracellular Vesicles". 2017; 2017
Institución organizadora:
International Society for Extracellular Vesicles
Resumen:
Introduction: Chronic T cell activation and dysfunction are hallmarks ofHIV infection. Taking into consideration that T cell metabolism influencesT cell functionality, we hypothesised that CD4+ T cell dysfunctionduring HIV infection could be associated to virus-induced metabolicalterations. A critical transcription factor in the coordination of T cellmetabolism, differentiation and effector function is Hypoxia induciblefactor-1 alpha (HIF-1). Herein, we analysed the role of extracellularvesicles in the bystander modulation of HIF-1 activity and CD4+ Tcell function during HIV infection.Methods: CD4+ T cells isolated from the blood of healthy donors wereinfected in vitro with HIV mutants unable to produce progeny viralparticles. Extracellular vesicles were isolated by differential centrifugationand/or analysed by immunocapture on CD63-coated beads followedby detection with fluorescently-labelled antibodies. The role of EVsreleased by HIV infected cells in bystander CD4+ T cell metabolismand function was assessed.Results: HIV-1 infection triggers HIF-1 expression and activity, promotingaerobic glycolysis and the production of the proinflammatory cytokinesIL-17A and interferon-gamma. Moreover, HIV-1 induces the HIF1-mediatedsecretion of Extracellular Vesicles. These vesicles, in turn,promote HIF-1 activity and the secretion of gamma-interferon inbystander cells.