Increased expression of negative regulators of cytokine signaling during chronic HIV disease cause functionally exhausted state of dendritic cells

Abstract Mechanisms of functional impairment of dendritic cells (DCs) during chronic HIV-1 infection are not well understood. In order to understand this phenomenon, we aimed to study the expression of negative regulators of cytokine signaling and correlate with DC exhaustion during chronic HIV-1 disease. Monocyte-derived DCs (mo-DCs) from 27 HIV-1 infected patients (CD4+ T-cell counts: 429 ± 44 cells/μL, plasma viral load: Log 10  3.9 ± 1.0 copies/ml) and 19 healthy controls (HCs) were stimulated ex vivo with TLR4 agonist, lipopolysaccharide (LPS) for 2 days to evaluate their functional fitness. The expression of a set of genes associated with cytokine signaling was evaluated in a custom designed PCR array by Real-Time PCR. The mo-DCs from HIV-1 infected patients depicted functional exhaustion as evident by decreased allo-stimulation index (mean ± SD: 10 ± 6 vs. 24 ± 16) (p