title: Potent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers.
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.
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America.
authors.forename: Enrique
authors.initials: E
authors.lastname: Martin-Gayo
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America; Infectious Disease Division, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Buzon
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America.
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Ouyang
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America.
authors.forename: Taylor
authors.initials: T
authors.lastname: Hickman
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Cronin
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America.
authors.forename: Dina
authors.initials: D
authors.lastname: Pimenova
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America; Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America; Infectious Disease Division, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Infectious Disease Division, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Mathias
authors.initials: M
authors.lastname: Lichterfeld
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America.
authors.forename: Xu G
authors.initials: XG
authors.lastname: Yu
mesh_terms: D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering
chemical_list: D034741:RNA, Small Interfering