Contrato Predoc en VIH/SIDA pFIS. Instituto de Biomedicina de Sevilla
Se busca candidato para solicitar contrato predoctoral de 3 años dentro del programa PFIS. El proyecto trata sobre inmunopatogenia en la infección por VIH. Se solicitan CV con nota media superior a 2.5 (8 sobre 10), opcionalmente con comunicaciones a congresos y/o publicaciones. Interesados enviar CV a: firstname.lastname@example.org antes del 10 de mayo.
Resumen del proyecto
Disturbances in the innate arm of immunity have important deleterious effects in aging and HIV-infection. Both scenarios are characterized by a low grade chronic inflammation related with age-associated diseases. In HIV-infection, these diseases are termed non AIDS events (NAEs); the main cause of mortality in HIV-infected patients on suppressive antiretroviral therapy (cART) (currently, 80-90% of the patients). In my group, we have observed in these patients that parameters associated with monocyte activation and specifically with the phenotype and functionality of these cells are deeply deregulated. A growing body of evidence indicates that another innate immunity component playing a critical role in HIV pathogenesis, is the plasmacytoid dendritic cell (pDC).These cells are the main type I Interferon (IFN-I) producers. pDCs sense virus and bacteria through endosomal Toll like receptors (TLRs)-7 and -9. Therefore, pDCs produce IFN which confers to this cell a high antiviral
capacity, activate antiviral host restriction factors and at the same time matures, expressing co-stimulatory molecules and become antigen presenting cells (APCs) enabling the expansion of CD4+ and CD8+ T-cells. This makes pDCs an essential link between innate and adaptive immunity. All this exhaustive coordinated process is severely disturbed by HIV for its own benefit. Key feature of this deregulation is an aberrant IFN production which misbalances an “antigen presenting pDC phenotype” in favor of an “IFN producing pDC phenotype”. The cellular basis of this process is not completely understood.
Hypothesis: Different characteristics of pDC phenotype and functions are associated with different disease outcomes in HIV infection. These special characteristics and functions of the pDC, linking innate and adaptive immunity, allow the spontaneous control of HIV. On the contrary, the deregulation of the pDC in typical progressors induces a permanent activation and hyperinflammation that eventually favor the appearance of NAEs.
Objective: To analyze differential phenotypic and functional mechanisms of pDCs associated with different disease outcomes in HIV infection.
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