Intestinal monocytes and macrophages are required for T cell polarization in response to Citrobacter rodentium.
Intestinal monocytes and macrophages are required for T cell polarization in response to Citrobacter rodentium.
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DOI：
10.1084/jem.20130903
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发表时间：
2013-09-23
期刊：
影响因子：
--
通讯作者：
Nussenzweig MC
中科院分区：
文献类型：
--
作者：
Schreiber HA;Loschko J;Karssemeijer RA;Escolano A;Meredith MM;Mucida D;Guermonprez P;Nussenzweig MC
使用新的小鼠模型，单核细胞和巨噬细胞的特异性删除表明，虽然不需要启动对啮齿类柠檬酸杆菌的免疫，但它们有助于通过分泌 IL-12 来诱导 IFN-γ+ Th1 极化的适应性反应。树突状细胞 (DC)、单核细胞和巨噬细胞是密切相关的吞噬细胞，它们具有许多表型特征，并且在某些情况下具有共同的发育起源。尽管人们充分认识到树突状细胞在启动适应性免疫反应中的需要，但单核细胞和巨噬细胞的作用在很大程度上仍然不明确，部分原因是缺乏能够特异性消除它们的遗传工具。在这里，我们描述了一种双基因方法，需要 LysM 和 Csf1r 的重叠表达来定义和消耗单核细胞和巨噬细胞。通过啮齿类柠檬酸杆菌感染期间单核细胞和巨噬细胞的选择性消耗来测试单核细胞和巨噬细胞在病原体免疫中的作用。虽然这两种细胞类型都不需要启动免疫，但单核细胞和巨噬细胞通过分泌 IL-12 促进适应性免疫反应，IL-12 诱导 Th1 极化和 IFN-γ 分泌。因此，尽管 DC 对于启动初始 CD4+ T 细胞是必不可少的，但单核细胞和巨噬细胞通过产生指导 T 细胞极化的介质来参与肠道免疫。
Using a new mouse model, the specific deletion of monocytes and macrophages reveals that, although not required to initiate immunity to Citrobacter rodentium, they contribute to the adaptive response via IL-12 secretion to induced IFN-γ+ Th1 polarization. Dendritic cells (DCs), monocytes, and macrophages are closely related phagocytes that share many phenotypic features and, in some cases, a common developmental origin. Although the requirement for DCs in initiating adaptive immune responses is well appreciated, the role of monocytes and macrophages remains largely undefined, in part because of the lack of genetic tools enabling their specific depletion. Here, we describe a two-gene approach that requires overlapping expression of LysM and Csf1r to define and deplete monocytes and macrophages. The role of monocytes and macrophages in immunity to pathogens was tested by their selective depletion during infection with Citrobacter rodentium. Although neither cell type was required to initiate immunity, monocytes and macrophages contributed to the adaptive immune response by secreting IL-12, which induced Th1 polarization and IFN-γ secretion. Thus, whereas DCs are indispensable for priming naive CD4+ T cells, monocytes and macrophages participate in intestinal immunity by producing mediators that direct T cell polarization.
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影响因子：
4.4
作者：
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