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

Meier,A, Chang,JJ, Chan,ES, Pollard,RB, Sidhu,HK, Kulkarni,S, Wen,TF, Lindsay,RJ, Orellana,L, Mildvan,D, Bazner,S, Streeck,H, Alter,G, Lifson,JD, Carrington,M, Bosch,RJ, Robbins,GK and Altfeld,M 2009, Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1, Nature medicine, vol. 15, no. 8, pp. 955-959, doi: 10.1038/nm.2004.

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Title Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1
Author(s) Meier,A
Orellana,LORCID iD for Orellana,L
Journal name Nature medicine
Volume number 15
Issue number 8
Start page 955
End page 959
Publisher Nature Publishing Group
Place of publication New York, NY
Publication date 2009-08
ISSN 1078-8956
Summary 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.
Language eng
DOI 10.1038/nm.2004
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2008, Nature Publishing Group
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Document type: Journal Article
Collection: Faculty of Health
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