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

TitlePotent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers.
Publication TypeJournal Article
Year of Publication2015
AuthorsMartin-Gayo E, Buzon MJose, Ouyang Z, Hickman T, Cronin J, Pimenova D, Walker BD, Lichterfeld M, Yu XG
JournalPLoS Pathog
Volume11
Issue6
Paginatione1004930
Date Published06/11/2015
ISSN1553-7374
Abstract

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.

DOI10.1371/journal.ppat.1004930
Alternate JournalPLoS Pathog.
PubMed ID26067651
PubMed Central IDPMC4466270
Grant List5P30AI060354-10 / AI / NIAID NIH HHS / United States
AI078799 / AI / NIAID NIH HHS / United States
AI087452 / AI / NIAID NIH HHS / United States
AI089339 / AI / NIAID NIH HHS / United States
AI098484 / AI / NIAID NIH HHS / United States
AI098487 / AI / NIAID NIH HHS / United States
AI106468 / AI / NIAID NIH HHS / United States
AI116228 / AI / NIAID NIH HHS / United States
HL121890 / HL / NHLBI NIH HHS / United States
HL126554 / HL / NHLBI NIH HHS / United States
R21 AI106468 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
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