Effects of HIV-1-induced CD1c and CD1d modulation and endogenous lipid presentation on CD1c-restricted T-cell activation.

Effects of HIV-1-induced CD1c and CD1d modulation and endogenous lipid presentation on CD1c-restricted T-cell activation.
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DOI:
10.1186/1471-2172-14-4
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发表时间:
2013-01-24
期刊:
影响因子:
3
通讯作者:
Tsuji M
Tsuji M
中科院分区:
医学4区
文献类型:
--
作者:
Kelly H;Mandraju R;Coelho-dos-Reis JG;Tsuji M

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已有研究表明,人类免疫缺陷病毒(HIV)-1感染可诱导有效产生病毒所需的内源性脂质的产生,而HIV-1感染下调了分化簇(CD)1分子CD1d的表达。然而,内源性脂质递呈的作用和HIV-1感染对CD1下调的影响尚未被表征。在这项研究中,我们观察到CD1c和CD1d的表达通过VPU依赖和Nef不依赖的机制下调,伴随而来的HIV-1诱导的宿主胆固醇的产生减少了CD1c和CD1d的调节程度。虽然艾滋病毒-1感染对CD1c的适度下调降低了CD1c限制的T细胞反应和分泌干扰素-γ的能力,但艾滋病毒-1感染同一细胞中胆固醇的上调似乎限制了CD1c的下调。HIV-1介导的CD1c表达的两个相互冲突的变化似乎最小化了CD1c表达的调节,从而导致宿主维持CD1c限制的T细胞对HIV-1的反应。
It has been shown that human immunodeficiency virus (HIV)-1 infection induces the production of endogenous lipids required for effective viral production, and the cluster of differentiation (CD)1 molecule CD1d is downregulated by HIV-1 infection. However, the role of endogenous lipid presentation and the implications of CD1 downregulation by HIV-1 infection have not yet been characterized. In this study, we observed downregulation of both CD1c and CD1d expression through a Vpu-dependent and Nef-independent mechanism, and the concomitant HIV-1-induced production of host cholesterol decreased the extent of CD1c and CD1d modulation. While the modest downregulation of CD1c by HIV-1 infection decreased the ability of CD1c-restricted T cells to respond and secrete interferon-γ, the cholesterol upregulation in the same cells by HIV-1 infection appears to limit the downregulation of CD1c. The two conflicting HIV-1-mediated changes in CD1c expression appear to minimize the modulation of CD1c expression, thus leading the host to maintain a CD1c-restricted T-cell response against HIV-1.
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