PPARγ and LXR Signaling Inhibit Dendritic Cell-Mediated HIV-1 Capture and trans-Infection

• DOI: 10.1371/journal.ppat.1000981
• Publication Date: 2010-07-01T21:04:48Z
• Authors: Timothy M. Hanley; Wendy Blay Puryear; Suryaram Gummuluru; Gregory A. Viglianti
• Keywords: Liver X receptor

Dendritic cells (DCs) contribute to human immunodeficiency virus type 1 (HIV-1) transmission and dissemination by capturing transporting infectious from the mucosa draining lymph nodes, transferring these particles CD4+ T with high efficiency. Toll-like receptor (TLR)-induced maturation of DCs enhances their ability mediate trans-infection migrate site infection. Because TLR-induced can be inhibited nuclear (NR) signaling, we hypothesized that ligand-activated NRs could repress DC-mediated HIV-1 dissemination. Here, show ligands for peroxisome proliferator-activated gamma (PPARγ) liver X (LXR) prevented proinflammatory cytokine production DC migration in response chemokine CCL21 preventing upregulation CCR7. Importantly, PPARγ LXR signaling both immature mature capture independent viral envelope glycoprotein. induced cholesterol efflux led a decrease DC-associated cholesterol, which has previously been shown required HIV-1. Finally, repletion targeted knockdown transport protein ATP-binding cassette A1 (ABCA1) restored NR ligand treated transfer it cells. Our results suggest up-regulate ABCA1-mediated this accounts decreased The mediated trans-infection, inflammation, underscores potential therapeutic value inhibiting mucosal transmission.