Differential expression of IFN-α and TRAIL/DR5 in lymphoid tissue of progressor versus nonprogressor HIV-1-infected patients

Loss of CD4(+) T cells, the hallmark of HIV pathogenesis, was suggested to be partly due to apoptosis. We recently reported that IFN-alpha produced by HIV-1-activated plasmacytoid dendritic cells (pDCs) contributes to CD4(+) T cell apoptosis by the TNF-related apoptosis-inducing ligand (TRAIL)/death receptor (DR)5 pathway. Here, we show that HIV-1-induced intracellular expression of IFN-alpha in pDCs is coupled to increased expression of IFN regulatory factor 7 and MyD88 by pDCs in vivo and in vitro. Expression of IFN-a was increased in lymphoid tonsillar tissue (LT) of patients with progressive (HIVprog) compared with nonprogressive (HIVNP) HIV-1 disease and to uninfected controls. LT from HIVprog exhibited higher TRAIL and DR5 mRNA levels than LT from HIVNP or controls. TRAIL mRNA levels in LT correlated with plasma viral load. We show that HIV-1 induces IFN-alpha and the TRAIL/DR5 apoptotic pathway in LT, suggesting a role for these cytokines in HIV-1 immunopathogenesis.