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

PLoS Pathogens

Xu G. Yu¹  Zhengyu Ouyang²  Enrique Martin-Gayo³  Dina Pimenova³  Maria Jose Buzon³  Mathias Lichterfeld³  Taylor Hickman³  Jacqueline Cronin³  Bruce D. Walker³ 

[1] Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America;Infectious Disease Division, Massachusetts General Hospital, Boston, Massachusetts, United States of America;Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America

关键词: HIV-1;    Immune response;    T cells;    Interferons;    Secretion;    Cytotoxic T cells;    Gene expression;    Highly-active antiretroviral therapy;   

DOI  :  10.1371/journal.ppat.1004930

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY