Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1.
Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1.
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作者：
妇女和男子的病毒感染表现可能不同，在艾滋病毒-1疾病的病程中也有显著的性别差异。感染HIV-1的妇女在HIV-1感染早期的病毒载量水平往往较低，但在给定的病毒载量下，比男子更快地发展为艾滋病。在这里，我们证明了浆细胞样树突状细胞（pDC）对HIV-1的反应存在显著的性别差异。与来自男性的pDC相比，来自女性的pDC响应于HIV-1编码的TLR 7配体产生显著更多的干扰素-α（IFN-α），导致更强的CD 8 + T细胞的次级活化。与这些体外研究一致，在调整病毒载量后，未经治疗的慢性HIV-1感染女性的CD 8 + T细胞活化水平显著高于男性。这些数据表明，TLR介导的pDC活化的性别差异可以解释在给定的HIV-1病毒载量下女性比男性更高的免疫活化，并提供了一种机制，通过该机制，相同水平的病毒复制可能导致女性比男性更快的HIV-1疾病进展。因此，pDC中TLR 7通路的调节可能代表了减少HIV-1相关病理的新方法。
Manifestations of viral infections can differ between women and men, and significant sex differences have been described in the course of HIV-1 disease. HIV-1-infected women tend to have lower viral load levels early in HIV-1 infection, but progress faster to AIDS for a given viral load than men. Here we demonstrate substantial sex differences in the response of plasmacytoid dendritic cells (pDCs) to HIV-1. pDCs derived from women produce significantly more interferon-α (IFN-α) in response to HIV-1-encoded TLR7 ligands than pDCs derived from men, resulting in stronger secondary activation of CD8+ T cells. In line with these in vitro studies, treatment-naïve chronically HIV-1-infected women had significantly 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 can 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 novel approach to reduce HIV-1-associated pathology.
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DOI：
10.1038/nri2394
发表时间：
2008-09
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Fish EN
通讯作者：
Fish EN
DOI：
10.1073/pnas.0600363103
发表时间：
2006-05-02
影响因子：
11.1
作者：
Herbeuval, JP;Nilsson, J;Shearer, GM
通讯作者：
Shearer, GM
DOI：
10.1097/01.qai.0000226789.51992.3f
发表时间：
2006-08-01
影响因子：
3.6
作者：
Gandhi, Rajesh T.;Spritzler, John;Pollard, Richard B.
通讯作者：
Pollard, Richard B.
影响因子：
6.4
作者：
Hunt, Peter W.;Brenchley, Jason;Deeks, Steven G.
通讯作者：
Deeks, Steven G.
影响因子：
158.5
作者：
FAHEY, JL;TAYLOR, JMG;GIORGI, JV
通讯作者：
GIORGI, JV