Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1.
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.
Meier
Angela
A
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, Massachusetts, USA.
Chang
J Judy
JJ
Chan
Ellen S
ES
Pollard
Richard B
RB
Sidhu
Harlyn K
HK
Kulkarni
Smita
S
Wen
Tom Fang
TF
Lindsay
Robert J
RJ
Orellana
Liliana
L
Mildvan
Donna
D
Bazner
Suzane
S
Streeck
Hendrik
H
Alter
Galit
G
Lifson
Jeffrey D
JD
Carrington
Mary
M
Bosch
Ronald J
RJ
Robbins
Gregory K
GK
Altfeld
Marcus
M
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D011374:Progesterone / Q000097:blood; D012727:Sex Characteristics; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D019562:Viral Load
D016898:Interferon-alpha; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D011374:Progesterone