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Sex differences in the Toll-like receptor–mediated response of plasmacytoid dendritic cells to HIV-1
Open accessAbstract
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.
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“These results point out that sex differences observed in the progression of HIV-1 may be due to stronger immune responses in women, which present higher activation of pDCs induced by TLR compared tomen at a given viral load (77).”
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Metadata
- Authors
- Meier, A., Chang, J. J., Chan, E. S., Pollard, R. B., Sidhu, H. K., Kulkarni, S., Wen, T. F., Lindsay, R. J., Orellana, L., Mildvan, D., Bazner, S., Streeck, H., Alter, G., Lifson, J. D., Carrington, M., Bosch, R. J., Robbins, G. K., & Altfeld, M.
- Venue
- Nature Medicine
- Published
- 2009-07-13
- Volume
- 15
- Issue
- 8
- Pages
- 955-959
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2027798298
- Cited by
- 594
- References
- 0
- FWCI
- 13.92
- Type
- journal article
- Language
- en
- Open access
- green
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