Modeling the immune rheostat of macrophages in the lung in response to infection
Modeling the immune rheostat of macrophages in the lung in response to infection
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DOI：
10.1073/pnas.0904846106
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发表时间：
2009-07-07
影响因子：
11.1
通讯作者：
Schlesinger, Larry S.
中科院分区：
文献类型：
--
作者：
Day, Judy;Friedman, Avner;Schlesinger, Larry S.
在肺中，交替激活的巨噬细胞（AAM）形成了抵抗微生物感染的第一道防线。由于AAM的高度调节性质，肺可以被认为是呼吸道病原体的免疫抑制器官。然而，随着肺部感染的进展，另一群巨噬细胞（称为经典活化巨噬细胞（CAM））进入;这些细胞通常被IFN-γ激活。CAM在清除微生物负荷、产生促炎细胞因子和产生足够免疫应答所必需的抗菌防御机制方面比AAM有效得多。在这里，我们关心的是确定第一次时，人口的CAM变得更占主导地位，比人口的AAM。在结核分枝杆菌（MTb）感染的背景下探索了所提出的“转换时间”。我们已经开发了一个数学模型，该模型描述了AAM和CAM激活中涉及的细胞、细菌和细胞因子之间的相互作用。该模型，基于微分方程系统，是一个有用的工具来分析减少切换时间的策略，并产生实验测试的假设。
In the lung, alternatively activated macrophages (AAM) form the first line of defense against microbial infection. Due to the highly regulated nature of AAM, the lung can be considered as an immunosuppressive organ for respiratory pathogens. However, as infection progresses in the lung, another population of macrophages, known as classically activated macrophages (CAM) enters; these cells are typically activated by IFN-gamma. CAM are far more effective than AAM in clearing the microbial load, producing proinflammatory cytokines and antimicrobial defense mechanisms necessary to mount an adequate immune response. Here, we are concerned with determining the first time when the population of CAM becomes more dominant than the population of AAM. This proposed "switching time'' is explored in the context of Mycobacterium tuberculosis (MTb) infection. We have developed a mathematical model that describes the interactions among cells, bacteria, and cytokines involved in the activation of both AAM and CAM. The model, based on a system of differential equations, represents a useful tool to analyze strategies for reducing the switching time, and to generate hypotheses for experimental testing.