Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections
Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections
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DOI：
10.1038/nm.1871
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发表时间：
2008-10-01
期刊：
影响因子：
82.9
通讯作者：
Feinberg, Mark B.
中科院分区：
文献类型：
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作者：
Mandl, Judith N.;Barry, Ashley P.;Feinberg, Mark B.
人类的病原性HIV感染和恒河猴的猴免疫缺陷病毒（SIV）感染的特征是全身性免疫激活和进行性CD 4（+）T细胞耗竭。相反，SIV的天然储存宿主，如白眉猴，尽管SIV复制水平很高，但不会发展为艾滋病，并且缺乏异常的免疫激活和保存的CD 4（+）T细胞群。在这里，我们表明，在急性和慢性SIV感染期间，白眉白眉猴体内先天免疫系统激活水平显著降低，并且白眉猴浆细胞样树突状细胞（pDC）在体外对SIV和其他Toll样受体7和9配体的应答中产生的干扰素-α明显减少。我们认为，在非自然宿主中SIV和HIV对pDC的慢性刺激可能会导致持续的免疫系统激活和功能障碍，这是艾滋病进展的基础。这种病毒连续复制和免疫病理学的恶性循环在自然界的白眉猴宿主中是不存在的。
Pathogenic HIV infections of humans and simian immunodeficiency virus (SIV) infections of rhesus macaques are characterized by generalized immune activation and progressive CD4(+) T cell depletion. In contrast, natural reservoir hosts for SIV, such as sooty mangabeys, do not progress to AIDS and show a lack of aberrant immune activation and preserved CD4(+) T cell populations, despite high levels of SIV replication. Here we show that sooty mangabeys have substantially reduced levels of innate immune system activation in vivo during acute and chronic SIV infection and that sooty mangabey plasmacytoid dendritic cells (pDCs) produce markedly less interferon-a in response to SIV and other Toll-like receptor 7 and 9 ligands ex vivo. We propose that chronic stimulation of pDCs by SIV and HIV in non-natural hosts may drive the unrelenting immune system activation and dysfunction underlying AIDS progression. Such a vicious cycle of continuous virus replication and immunopathology is absent in natural sooty mangabey hosts.