Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1

Angela Meier, J. Judy Chang, Ellen S. Chan, Richard B. Pollard, Harlyn K. Sidhu, Smita Kulkarni, Tom Fang Wen, Robert J. Lindsay, Liliana Orellana, Donna Mildvan, Suzane Bazner, Hendrik Streeck, Galit Alter, Jeffrey D. Lifson, Mary Carrington, Ronald J. Bosch, Gregory K. Robbins, Marcus Altfeld

Research output: Contribution to journalArticlepeer-review

455 Scopus citations


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.

Original languageEnglish
Pages (from-to)955-959
Number of pages5
JournalNature Medicine
Issue number8
StatePublished - Aug 2009
Externally publishedYes


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