PMID- 20617179
OWN - NLM
STAT- MEDLINE
DCOM- 20101123
LR  - 20211020
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 6
IP  - 7
DP  - 2010 Jul 1
TI  - PPARgamma and LXR signaling inhibit dendritic cell-mediated HIV-1 capture and 
      trans-infection.
PG  - e1000981
LID - 10.1371/journal.ppat.1000981 [doi]
LID - e1000981
AB  - Dendritic cells (DCs) contribute to human immunodeficiency virus type 1 (HIV-1) 
      transmission and dissemination by capturing and transporting infectious virus 
      from the mucosa to draining lymph nodes, and transferring these virus particles 
      to CD4+ T cells with high efficiency. Toll-like receptor (TLR)-induced maturation 
      of DCs enhances their ability to mediate trans-infection of T cells and their 
      ability to migrate from the site of infection. Because TLR-induced maturation can 
      be inhibited by nuclear receptor (NR) signaling, we hypothesized that 
      ligand-activated NRs could repress DC-mediated HIV-1 transmission and 
      dissemination. Here, we show that ligands for peroxisome proliferator-activated 
      receptor gamma (PPARgamma) and liver X receptor (LXR) prevented proinflammatory 
      cytokine production by DCs and inhibited DC migration in response to the 
      chemokine CCL21 by preventing the TLR-induced upregulation of CCR7. Importantly, 
      PPARgamma and LXR signaling inhibited both immature and mature DC-mediated 
      trans-infection by preventing the capture of HIV-1 by DCs independent of the 
      viral envelope glycoprotein. PPARgamma and LXR signaling induced cholesterol 
      efflux from DCs and led to a decrease in DC-associated cholesterol, which has 
      previously been shown to be required for DC capture of HIV-1. Finally, both 
      cholesterol repletion and the targeted knockdown of the cholesterol transport 
      protein ATP-binding cassette A1 (ABCA1) restored the ability of NR ligand treated 
      cells to capture HIV-1 and transfer it to T cells. Our results suggest that 
      PPARgamma and LXR signaling up-regulate ABCA1-mediated cholesterol efflux from 
      DCs and that this accounts for the decreased ability of DCs to capture HIV-1. The 
      ability of NR ligands to repress DC mediated trans-infection, inflammation, and 
      DC migration underscores their potential therapeutic value in inhibiting HIV-1 
      mucosal transmission.
FAU - Hanley, Timothy M
AU  - Hanley TM
AD  - Department of Microbiology, Boston University School of Medicine, Boston, 
      Massachusetts, United States of America.
FAU - Blay Puryear, Wendy
AU  - Blay Puryear W
FAU - Gummuluru, Suryaram
AU  - Gummuluru S
FAU - Viglianti, Gregory A
AU  - Viglianti GA
LA  - eng
GR  - T32-AI0764206/AI/NIAID NIH HHS/United States
GR  - F32-AI084558/AI/NIAID NIH HHS/United States
GR  - F32 AI084558/AI/NIAID NIH HHS/United States
GR  - R01 AI064099/AI/NIAID NIH HHS/United States
GR  - R21 AI081596/AI/NIAID NIH HHS/United States
GR  - R01 AI073149/AI/NIAID NIH HHS/United States
GR  - T32-AI07309/AI/NIAID NIH HHS/United States
GR  - AI064099/AI/NIAID NIH HHS/United States
GR  - T32 AI007309/AI/NIAID NIH HHS/United States
GR  - AI073149/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100701
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (ABCA1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter 1)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (CCL21 protein, human)
RN  - 0 (Chemokine CCL21)
RN  - 0 (Liver X Receptors)
RN  - 0 (Orphan Nuclear Receptors)
RN  - 0 (PPAR gamma)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - ATP Binding Cassette Transporter 1
MH  - ATP-Binding Cassette Transporters/genetics/physiology
MH  - Cell Movement/drug effects
MH  - Chemokine CCL21/physiology
MH  - Cholesterol/metabolism
MH  - Dendritic Cells/physiology/*virology
MH  - HIV Infections/*transmission
MH  - HIV-1/physiology
MH  - Humans
MH  - Liver X Receptors
MH  - Orphan Nuclear Receptors/*physiology
MH  - PPAR gamma/*physiology
MH  - Receptors, Cytoplasmic and Nuclear/physiology
MH  - Signal Transduction
MH  - Up-Regulation
PMC - PMC2895661
COIS- The authors have declared that no competing interests exist.
EDAT- 2010/07/10 06:00
MHDA- 2010/12/14 06:00
PMCR- 2010/07/01
CRDT- 2010/07/10 06:00
PHST- 2009/10/06 00:00 [received]
PHST- 2010/06/02 00:00 [accepted]
PHST- 2010/07/10 06:00 [entrez]
PHST- 2010/07/10 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
PHST- 2010/07/01 00:00 [pmc-release]
AID - 09-PLPA-RA-1789R3 [pii]
AID - 10.1371/journal.ppat.1000981 [doi]
PST - epublish
SO  - PLoS Pathog. 2010 Jul 1;6(7):e1000981. doi: 10.1371/journal.ppat.1000981.