Integrative model of the immune response to a pulmonary macrophage infection: what determines the infection duration?
Integrative model of the immune response to a pulmonary macrophage infection: what determines the infection duration?
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DOI：
10.1371/journal.pone.0107818
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Touzeau S
中科院分区：
文献类型：
--
作者：
Go N;Bidot C;Belloc C;Touzeau S
决定病原体针对肺巨噬细胞的感染持续时间的免疫机制尚不清楚。要探索这些病原菌的影响，必须整合各种免疫机制，并考虑病原菌毒力和寄主敏感性的差异性。在这种背景下，数学模型是对实验的补充，是描述和探索感染和免疫动力学中涉及的复杂机制的强大工具。我们开发了一个原始的数学模型，其中我们详细描述了巨噬细胞和病原体之间的相互作用，适应性反应的方向和细胞因子的调节。我们将我们的模型应用于猪呼吸与生殖综合征病毒(PRRSV)，这是养猪业的主要关注点。我们从呼吸道病原体的建模和实验研究中提取了模型参数的取值范围。我们通过敏感度分析确定了影响最大的参数。我们定义了一个参数集，即参考场景，从而产生了对PRRSV感染的现实和具有代表性的免疫反应。然后，我们定义了与参考情景周围的菌株毒力和宿主敏感性的分级水平相对应的情景。我们观察到，高水平的抗病毒细胞因子和显性细胞反应与通常假设的短感染持续时间或长感染持续时间相关，这取决于涉及的免疫机制。为了确定这些机制，我们需要结合抗病毒细胞因子的水平，包括和。后者是感染巨噬细胞水平的良好指标，两者结合起来提供适应性反应方向。现有的PRRSV疫苗缺乏效力。通过整合复杂免疫机制之间的主要相互作用，该建模框架可用于帮助设计更有效的疫苗接种策略。
The immune mechanisms which determine the infection duration induced by pathogens targeting pulmonary macrophages are poorly known. To explore the impact of such pathogens, it is indispensable to integrate the various immune mechanisms and to take into account the variability in pathogen virulence and host susceptibility. In this context, mathematical models complement experimentation and are powerful tools to represent and explore the complex mechanisms involved in the infection and immune dynamics. We developed an original mathematical model in which we detailed the interactions between the macrophages and the pathogen, the orientation of the adaptive response and the cytokine regulations. We applied our model to the Porcine Respiratory and Reproductive Syndrome virus (PRRSv), a major concern for the swine industry. We extracted value ranges for the model parameters from modelling and experimental studies on respiratory pathogens. We identified the most influential parameters through a sensitivity analysis. We defined a parameter set, the reference scenario, resulting in a realistic and representative immune response to PRRSv infection. We then defined scenarios corresponding to graduated levels of strain virulence and host susceptibility around the reference scenario. We observed that high levels of antiviral cytokines and a dominant cellular response were associated with either short, the usual assumption, or long infection durations, depending on the immune mechanisms involved. To identify these mechanisms, we need to combine the levels of antiviral cytokines, including , and . The latter is a good indicator of the infected macrophage level, both combined provide the adaptive response orientation. Available PRRSv vaccines lack efficiency. By integrating the main interactions between the complex immune mechanisms, this modelling framework could be used to help designing more efficient vaccination strategies.
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影响因子：
3.7
作者：
Dobrovolny HM;Reddy MB;Kamal MA;Rayner CR;Beauchemin CA
通讯作者：
Beauchemin CA
影响因子：
3.3
作者：
Gomez-Laguna, Jaime;Rodriguez-Gomez, Irene M.;Carrasco, Librado
通讯作者：
Carrasco, Librado
DOI：
10.1016/j.tvjl.2012.11.012
发表时间：
2013-03
期刊：
Veterinary journal (London, England : 1997)
影响因子：
--
作者：
Gómez-Laguna J;Salguero FJ;Pallarés FJ;Carrasco L
通讯作者：
Carrasco L
DOI：
10.1038/nri3166
发表时间：
2012-03-09
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
猪生殖和呼吸道综合征病毒感染中同源和异源适应性免疫反应的表征。
影响因子：
4.4
作者：
Díaz I;Gimeno M;Darwich L;Navarro N;Kuzemtseva L;López S;Galindo I;Segalés J;Martín M;Pujols J;Mateu E
通讯作者：
Mateu E