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- Title
Sex differences in the Toll-like receptor–mediated response of plasmacytoid dendritic cells to HIV-1.
- Authors
Meier, Angela; Chang, J. Judy; Chan, Ellen S.; Pollard, Richard B.; Sidhu, Harlyn K.; Kulkarni, Smita; Wen, Tom Fang; Lindsay, Robert J.; Orellana, Liliana; Mildvan, Donna; Bazner, Suzane; Streeck, Hendrik; Alter, Galit; Lifson, Jeffrey D.; Carrington, Mary; Bosch, Ronald J.; Robbins, Gregory K.; Altfeld, Marcus
- Abstract
Manifestations of viral infections can differ between women and men, and marked sex differences have been described in the course of HIV-1 disease. HIV-1–infected women tend to have lower viral loads early in HIV-1 infection but progress faster to AIDS for a given viral load than men. Here we show substantial sex differences in the response of plasmacytoid dendritic cells (pDCs) to HIV-1. pDCs derived from women produce markedly more interferon-α (IFN-α) in response to HIV-1–encoded Toll-like receptor 7 (TLR7) ligands than pDCs derived from men, resulting in stronger secondary activation of CD8+ T cells. In line with these in vitro studies, treatment-naive women chronically infected with HIV-1 had considerably higher levels of CD8+ T cell activation than men after adjusting for viral load. These data show that sex differences in TLR-mediated activation of pDCs may account for higher immune activation in women compared to men at a given HIV-1 viral load and provide a mechanism by which the same level of viral replication might result in faster HIV-1 disease progression in women compared to men. Modulation of the TLR7 pathway in pDCs may therefore represent a new approach to reduce HIV-1–associated pathology.
- Subjects
VIRUS diseases; HIV infections; SEX differences (Biology); HIV-positive women; VIRAL replication; INTERFERONS; PATHOLOGY
- Publication
Nature Medicine, 2009, Vol 15, Issue 8, p955
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm.2004