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

TitleSex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1.
Publication TypeJournal Article
Year of Publication2009
AuthorsMeier A, J Chang J, Chan ES, Pollard RB, Sidhu HK, Kulkarni S, Wen TFang, Lindsay RJ, Orellana L, Mildvan D, Bazner S, Streeck H, Alter G, Lifson JD, Carrington M, Bosch RJ, Robbins GK, Altfeld M
JournalNat Med
Volume15
Issue8
Pagination955-9
Date Published2009 Aug
ISSN1546-170X
KeywordsAdult, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Dendritic Cells, Female, HIV Infections, HIV-1, Humans, Interferon-alpha, Lymphocyte Activation, Male, Progesterone, Sex Characteristics, Toll-Like Receptor 7, Viral Load
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-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.

DOI10.1038/nm.2004
Alternate JournalNat. Med.
PubMed ID19597505
PubMed Central IDPMC2821111
Grant ListAI25879 / AI / NIAID NIH HHS / United States
AI27659 / AI / NIAID NIH HHS / United States
AI27666 / AI / NIAID NIH HHS / United States
AI38855 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
HHSN261200800001E / / PHS HHS / United States
K01AI062435 / AI / NIAID NIH HHS / United States
P01 AI074415 / AI / NIAID NIH HHS / United States
P01 AI074415 / AI / NIAID NIH HHS / United States
P01 AI074415-01A2 / AI / NIAID NIH HHS / United States
P01 AI074415-01A20001 / AI / NIAID NIH HHS / United States
R21 AI071806 / AI / NIAID NIH HHS / United States
R21 AI071806 / AI / NIAID NIH HHS / United States
R21 AI071806-01A2 / AI / NIAID NIH HHS / United States
R21 AI071806-02 / AI / NIAID NIH HHS / United States