Potent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers

The majority of hiv-1 elite controllers (ec) restrict hiv-1 replication through highly functional hiv-1-specific t cell responses,but mechanisms supporting the evolution of effective hiv-1-specific t cell immunity in these patients remain undefined. cytosolic immune recognition of hiv-1 in conventional dendritic cells (cdc) can facilitate priming and expansion of hiv-1-specific t cells; however,hiv-1 seems to be able to avoid intracellular immune recognition in cdcs in most infected individuals. here,we show that exposure of cdcs from ec to hiv-1 leads to a rapid and sustained production of type i interferons and upregulation of several interferon-stimulated effector genes. emergence of these cell-intrinsic immune responses was associated with a reduced induction of samhd1 and ledgf/p75,and an accumulation of viral reverse transcripts,but inhibited by pharmacological blockade of viral reverse transcription or sirna-mediated silencing of the cytosolic dna sensor cgas. importantly,improved cell-intrinsic immune recognition of hiv-1 in cdcs from elite controllers translated into stronger abilities to stimulate and expand hiv-1-specific cd8 t cell responses. these data suggest an important role of cell-intrinsic type i interferon secretion in dendritic cells for the induction of effective hiv-1-specific cd8 t cells,and may be helpful for eliciting functional t cell immunity against hiv-1 for preventative or therapeutic clinical purposes. © 2015 martin-gayo et al.