Sex differences in the TLR-mediated response of pDCs to HIV-1 are associated with higher immune activation in infected women

By A. Meier, J. Chang, Ellen S. Chan, R. Pollard, Harlyn K. Sidhu, S. Kulkarni, T. F. Wen, R. Lindsay, L. Orellana, D. Mildvan and 8 more. Nature Medicine, 2009

599 citations recorded by the source corpus.

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.

Subfields: Immunology, Virology

View Paper: https://www.semanticscholar.org/paper/59960b0964822a46d401447bf010a67a16cf512e

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Citations in the corpus

• Sexual Dimorphism in Innate Immunity (2019, unknown): “pDCs derived from women produced significantly more IFN-α in response to HIV-1 encoded TLR7 ligands than pDCs derived from men, resulting in stronger secondary activation of CD8+ T cells [12].”
• Plasmacytoid Dendritic Cells: Recent Progress and Open Questions (2011, background): “, in female compared to male patients (120) or in primate species susceptible to simian immunodeficiency virus (121).”
• Sex-based differences in susceptibility to SARS-CoV infection (2017, background): “High copy numbers of TLR7 (located on the X-chromosome) and elevated IRF-7 expression in females induce increased IFN-b production by plasmacytoid dendritic cells and provided protection against HIV infection (42, 43).”
• Estrogen receptors regulate innate immune cells and signaling pathways (2015, background): “As mentioned above, pDCs from female HIV patients produce more IFNα than male pDCs [46].”