Letter abstract
Nature Medicine 15, 955 - 959 (2009)
Published online: 13 July 2009 | doi:10.1038/nm.2004
Sex differences in the Toll-like receptor–mediated response of plasmacytoid dendritic cells to HIV-1
Angela Meier1,8, J Judy Chang1,8, Ellen S Chan2, Richard B Pollard3, Harlyn K Sidhu1, Smita Kulkarni4, Tom Fang Wen1, Robert J Lindsay1, Liliana Orellana2, Donna Mildvan5, Suzane Bazner1,6, Hendrik Streeck1, Galit Alter1, Jeffrey D Lifson7, Mary Carrington4, Ronald J Bosch2, Gregory K Robbins6 & Marcus Altfeld1,6
Manifestations of viral infections can differ between women and men1, 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 men2, 3, 4, 5, 6, 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-
(IFN-) 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.
- Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, Massachusetts, USA.
- Harvard School of Public Health, Boston, Massachusetts, USA.
- University of California–Davis Medical Center, Sacramento, California, USA.
- Cancer and Inflammation Program, Laboratory of Experimental Immunology and Science Applications International Corporation–Frederick, National Cancer Institute, Frederick, Maryland, USA.
- Beth Israel Medical Center, New York, New York, USA.
- Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
- AIDS and Cancer Virus Program, Science Applications International Corporation–Frederick, National Cancer Institute, Frederick, Maryland, USA.
- These authors contributed equally to this work.
Correspondence to: Marcus Altfeld1,6 e-mail: maltfeld@partners.org
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