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

  1. Author:
    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.

  2. Author Address

    Meier, Angela, Chang, J. Judy, Sidhu, Harlyn K.; Wen, Tom Fang, Lindsay, Robert J.; Bazner, Suzane, Streeck, Hendrik, Alter, Galit, Altfeld, Marcus] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Chan, Ellen S.; Orellana, Liliana, Bosch, Ronald J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Pollard, Richard B.] Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. [Kulkarni, Smita, Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD 21701 USA. [Lifson, Jeffrey D.] NCI, Sci Applicat Int Corp Frederick, AIDS & Canc Virus Program, Frederick, MD 21701 USA. [Mildvan, Donna] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Bazner, Suzane, Robbins, Gregory K.; Altfeld, Marcus] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA.
    1. Year: 2009
  2. Journal: Nature Medicine
    1. 15
    2. 8
    3. Pages: 955-U161
  4. Type of Article: Article
  1. Abstract:

    Manifestations of viral infections can differ between women and men(1), 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(2-7). 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.

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  2. DOI: 10.1038/nm.2004
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