Role of cell-to-cell variability in activating a positive feedback antiviral response in human dendritic cells.
Role of cell-to-cell variability in activating a positive feedback antiviral response in human dendritic cells.
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DOI：
10.1371/journal.pone.0016614
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发表时间：
2011-02-08
期刊：
影响因子：
3.7
通讯作者：
Sealfon SC
中科院分区：
文献类型：
--
作者：
Hu J;Nudelman G;Shimoni Y;Kumar M;Ding Y;López C;Hayot F;Wetmur JG;Sealfon SC
在新城疫病毒感染人单核细胞来源的树突状细胞后的最初几个小时内，IFNB1的诱导率极低，分泌的I型干扰素反应低于ELISA检测的限度。然而，许多干扰素诱导的基因在这个时候被激活，例如DDX58(RIGI)，它在对病毒RNA的反应中诱导IFNB1。我们调查了早期诱导IFNBI是否只在一小部分感染细胞中导致低水平的干扰素分泌，然后在所有细胞中诱导干扰素反应基因。我们开发了一个基于代理的数学模型来研究IFNBI和DDX58的时间动力学。模拟表明，少量的早期反应细胞为DDX58-IFNBI正反馈环的有效和可控激活提供了一种机制。该模型预测了单细胞反应的分布，并通过单细胞mRNA测量证实了这一点。结果表明，细胞间较大的变异在早期的先天性免疫反应中起着重要作用，这种变异对于基于IFNB1的反馈环的有效激活是必不可少的。
In the first few hours following Newcastle disease viral infection of human monocyte-derived dendritic cells, the induction of IFNB1 is extremely low and the secreted type I interferon response is below the limits of ELISA assay. However, many interferon-induced genes are activated at this time, for example DDX58 (RIGI), which in response to viral RNA induces IFNB1. We investigated whether the early induction of IFNBI in only a small percentage of infected cells leads to low level IFN secretion that then induces IFN-responsive genes in all cells. We developed an agent-based mathematical model to explore the IFNBI and DDX58 temporal dynamics. Simulations showed that a small number of early responder cells provide a mechanism for efficient and controlled activation of the DDX58-IFNBI positive feedback loop. The model predicted distributions of single cell responses that were confirmed by single cell mRNA measurements. The results suggest that large cell-to-cell variation plays an important role in the early innate immune response, and that the variability is essential for the efficient activation of the IFNB1 based feedback loop.
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影响因子：
5.4
作者：
Saenz, Roberto A.;Quinlivan, Michelle;Gog, Julia R.
通讯作者：
Gog, Julia R.
影响因子：
3.4
作者：
Coppey, Mathieu;Berezhkovskii, Alexander M.;Shvartsman, Stanislav Y.
通讯作者：
Shvartsman, Stanislav Y.
影响因子：
16
作者：
Blake, William J.;Balazsi, Gbor;Collins, James J.
通讯作者：
Collins, James J.
DOI：
10.1073/pnas.1934678100
发表时间：
2003-09-16
影响因子：
11.1
作者：
Honda, K;Sakaguchi, S;Taniguchi, T
通讯作者：
Taniguchi, T
影响因子：
11.4
作者：
Marié, I;Durbin, JE;Levy, DE
通讯作者：
Levy, DE