Plasmacytoid Dendritic Cells (pDCs) From HIV Controllers Produce Interferon-α and Differentiate Into Functional Killer pDCs Under HIV Activation

Abstract

We demonstrate that, in response to HIV, pDCs from controller patients produce IFN-α, express membrane TRAIL, and induce apoptosis of T-cell lines.

Plasmacytoid Dendritic Cells Mediate Synergistic Effects of HIV and Lipopolysaccharide on CD27+IgD–Memory B Cell Apoptosis

“…The persistent secretion of type I IFN and TRAIL by pDCs has been implicated in CD4 T cell decline and HIV pathogenesis (11,42). Although chronic HIV infection is associated with reduced numbers and dysfunction of pDCs (43)(44)(45), pDCs are at least partially responsible for the increased production of TRAIL and type I IFN in HIV infection (11,46,47). In the current study, soluble CD4 and a coreceptor inhibitor reduced HIV-1 virions or gp120-mediated FasL production in pDCs, indicating a direct correlation between pDCs and mB cell apoptosis during HIV infection.…”

“…The tumor necrosis factor alpha (TNF-␣)/ tumor necrosis factor receptor (TNFR), TRAIL/DR5, Fas/Fas ligand (FasL), and Foxo3a cell death signaling pathways have been reported to play a role in HIV pathogenesis (7)(8)(9)(10). Plasmacytoid dendritic cells (pDCs) have been reported to produce TRAIL in response to HIV (mediated through type I interferon [IFN]) and play a role in T cell depletion in HIV infection (11). Additionally, there is evidence of a role for the Fas/FasL signaling pathway in B cell apoptosis in HIV disease (8).…”

Immune activation of human brain microvascular endothelial cells inhibits HIV replication in macrophages

“…[39][40][41] However, their numbers and ability to produce type I IFNs are significantly reduced by HIV infection. [42][43][44][45][46] Thus, an IFNmediated antiviral response mounted by nonimmune cells such as brain ECs is likely to be beneficial for CNS protection. Although two early studies reported that brain ECs could be infected with HIV, 3,47 our results showed that hCMEC/D3 cells were not susceptible to HIV infection (supplemental Figure 5), which is consistent with the majority of evidence.…”

Innate Immune Activity Correlates with CD4 T Cell-Associated HIV-1 DNA Decline during Latency-Reversing Treatment with Panobinostat

“…Moreover, the immune effects of HIV-1-specific CD8 T cells are likely to be weakened by mutational escape in targeted epitopes (18,19) and by possible inhibition through the intrinsic pharmacological effects of HDACi (20). Innate effector cell responses, preferentially mediated by natural killer (NK) cells and plasmacytoid dendritic cells (pDCs), may also have a role in restricting HIV-1 replication, as suggested by functional assays (21,22), correlative cohorts studies (23,24), immunogenetic associations (25), and in vivo experiments in animal models (26). However, the specific role of these cells in the context of pharmacological latency-reversing treatment remains unknown and represents an understudied area of investigation.…”