Martin-Gayo, EnriqueBuzon, Maria JoseOuyang, ZhengyuHickman, TaylorCronin, JacquelinePimenova, DinaWalker, BruceLichterfeld, MathiasYu, Xu G.2015-07-132015Martin-Gayo, Enrique, Maria Jose Buzon, Zhengyu Ouyang, Taylor Hickman, Jacqueline Cronin, Dina Pimenova, Bruce D. Walker, Mathias Lichterfeld, and Xu G. Yu. 2015. “Potent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers.” PLoS Pathogens 11 (6): e1004930. doi:10.1371/journal.ppat.1004930. http://dx.doi.org/10.1371/journal.ppat.1004930.1553-7366http://nrs.harvard.edu/urn-3:HUL.InstRepos:17295556The 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.en-USJournal Article2015-07-1310.1371/journal.ppat.1004930