Journal
NATURE MEDICINE
Volume 15, Issue 8, Pages 955-U161Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.2004
Keywords
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Funding
- US National Institutes of Health (NIH)-National Institute of Allergy Infectious Diseases [R21 AI071806, PO1 AI074415, K01AI062435]
- Harvard University Center for AIDS Research
- Bill & Melinda Gates Foundation
- Doris Duke Charitable Foundation
- German Research Society (Deutsche Forschungsgemeinschaft)
- National Health and Medical Research Council of Australia [519578]
- National Institute of Allergy and Infectious Diseases [AI38855, AI27659, AI38858, AI25879, AI27666]
- Agouron/Pfizer, Bristol Myers Squibb and GlaxoSmithKline
- US National Cancer Institute (NCI), NIH [HHSN261200800001E]
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Manifestations of viral infections can differ between women and men(1), 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(2-7). 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-alpha (IFN-alpha) 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.
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