Project Details
Projekt Print View

CD40L-mediated defect of the interferon system in HIV-1 infection

Subject Area Virology
Term from 2010 to 2012
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 165239902
 
The progress of HIV-1 infection is associated with a significant loss in plasmacytoid dendritic cell (PDC) counts and function. PDC, the major producers of type I interferons in the blood, are crucial in coordinating innate and adaptive immune responses in viral and bacterial infections. We have shown phenotypic and functional deficits in PDC of HIV-infected patients, which were restored at least partially by stimulation with a new Pclass CpG oligonucleotide. In a follow-up study, we have identified elevated levels of soluble and cellular CD40 ligand (CD40L) in HIV-1 infection, which reduced the IFNalpha production in vitro. Therefore, we hypothesize that the chronic immune stimulation, reflected by increased CD40L expression, is responsible for the silencing of PDC innate immune responses in HIV-1 infection. To verify this hypothesis, we will focus on three aspects: (i) characterize the effects of CD40L on the function and phenotype of PDC, (ii) obtain a comprehensive picture of PDC silencing via chip-based gene expression profiling and pathway analysis, and (iii) investigate the effects of low-dose corticoids on the expression of CD40 and CD40L in a translational study of HIV-infected patients. Thus, our study will target immune stimulation as a major factor of HIV-1 pathogenesis.
DFG Programme Research Grants
 
 

Additional Information

Textvergrößerung und Kontrastanpassung