The dual role of dendritic cells in the immune response to human immunodeficiency virus type 1 infection.
The dual role of dendritic cells in the immune response to human immunodeficiency virus type 1 infection.
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DOI：
10.1099/vir.0.83600-0
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发表时间：
2008-09
期刊：
影响因子：
--
通讯作者：
Kirschner DE
中科院分区：
文献类型：
--
作者：
Hogue IB;Bajaria SH;Fallert BA;Qin S;Reinhart TA;Kirschner DE
HIV-1和人类免疫系统之间复杂相互作用的许多方面仍然难以捉摸。我们的目标是研究这些相互作用，重点是树突状细胞（DC）的具体作用。DC增强HIV-1感染过程以及促进抗病毒免疫应答。我们探讨这些双重角色的含义。我们提出并分析了一个数学模型，描述了HIV-1，CD 4+和CD 8 + T细胞，和DC在人体淋巴结中相互作用的动态。我们验证了我们的模型对非人灵长类SIV实验数据和已发表的人类HIV-1数据的行为。我们的模型定性和定量地概括了临床HIV-1感染动态。我们对模型进行敏感性分析，以确定哪些机制强烈影响感染动力学。敏感性分析确定了有助于感染进展的系统相互作用，包括DC相关机制。我们比较了DC依赖性和DC非依赖性途径的CD 4 + T细胞感染。该模型预测，当活化的T辅助细胞数量较低时，DC对T细胞的同时引发和感染驱动早期感染动力学。此外，我们的模型预测，虽然DC功能的直接失败和由于CD 4 + T细胞帮助的损失而导致的间接失败都是感染动力学的重要贡献者，但我们的结果支持了前者对HIV-1免疫发病机制具有更显著影响的假设。
Many aspects of the complex interaction between HIV-1 and the human immune system remain elusive. Our objective is to study these interactions, focusing on the specific roles of dendritic cells (DCs). DCs enhance HIV-1 infection processes as well as promote an anti-viral immune response. We explore the implications of these dual roles. We present and analyse a mathematical model describing the dynamics of HIV-1, CD4+ and CD8+ T-cells, and DCs interacting in a human lymph node. We validate the behaviour of our model against non-human primate SIV experimental data and published human HIV-1 data. Our model qualitatively and quantitatively recapitulates clinical HIV-1 infection dynamics. We perform sensitivity analyses on the model to determine which mechanisms strongly affect infection dynamics. Sensitivity analysis identifies system interactions that contribute to infection progression, including DC-related mechanisms. We compare DC-dependent and DC-independent routes of CD4+ T-cell infection. The model predicts that simultaneous priming and infection of T cells by DCs drives early infection dynamics when activated T-helper cell numbers are low. Further, our model predicts that, while direct failure of DC function and an indirect failure due to loss of CD4+ T-cell help are both significant contributors to infection dynamics, our results support the hypothesis that the former has a more significant impact on HIV-1 immunopathogenesis.
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影响因子：
3.1
作者：
Fallert, BA;Reinhart, TA
通讯作者：
Reinhart, TA
影响因子：
5.4
作者：
Jekle, A;Kepler, OT;Goldsmith, MA
通讯作者：
Goldsmith, MA
DOI：
10.1097/00042560-200205010-00006
发表时间：
2002-05-01
期刊：
JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
影响因子：
--
作者：
Bajaria, SH;Webb, G;Kirschner, D
通讯作者：
Kirschner, D
影响因子：
1.6
作者：
Gorry, Paul R;Sterjovski, Jasminka;Wesselingh, Steven
通讯作者：
Wesselingh, Steven
影响因子：
5.5
作者：
Chougnet, Claire;Gessani, Sandra
通讯作者：
Gessani, Sandra