Macrophages Use Distinct Actin Regulators to Switch Engulfment Strategies and Ensure Phagocytic Plasticity In Vivo
Macrophages Use Distinct Actin Regulators to Switch Engulfment Strategies and Ensure Phagocytic Plasticity In Vivo
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DOI：
10.1016/j.celrep.2020.107692
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发表时间：
2020-05-26
期刊：
影响因子：
8.8
通讯作者：
Wood, Will
中科院分区：
文献类型：
--
作者：
Davidson, Andrew J.;Wood, Will
巨噬细胞不仅必须响应于一系列不同的刺激，如感染和细胞损伤，而且还在体内发现的多样和复杂的组织环境中执行吞噬作用。这需要高度的形态学可塑性，因此也需要高度的细胞骨架可塑性。在这里，我们使用特殊的遗传学和果蝇胚胎的体内成像研究巨噬细胞吞噬细胞的多功能性在凋亡尸体清除。我们发现，巨噬细胞的吞噬作用是非常强大的，由于他们拥有两种不同的吞噬模式，利用独家套件的肌动蛋白调节蛋白。“板状脂质体吞噬作用”是Arp 2/3复合物依赖性的，并允许细胞向凋亡尸体迁移并包裹凋亡尸体。或者，透明和Ena驱动丝状伪足吞噬作用以伸出并吸入碎片。巨噬细胞切换到“丝状伪足吞噬作用”以克服空间限制，提供必要的强大可塑性，以确保无论它们在体内遇到什么障碍，它们都能履行其关键的清除功能。
Macrophages must not only be responsive to an array of different stimuli, such as infection and cellular damage, but also perform phagocytosis within the diverse and complex tissue environments found in vivo. This requires a high degree of morphological and therefore cytoskeletal plasticity. Here, we use the exceptional genetics and in vivo imaging of Drosophila embryos to study macrophage phagocytic versatility during apoptotic corpse clearance. We find that macrophage phagocytosis is highly robust, arising from their possession of two distinct modes of engulfment that utilize exclusive suites of actin-regulatory proteins. "Lamellipodial phagocytosis" is Arp2/3-complex-dependent and allows cells to migrate toward and envelop apoptotic corpses. Alternatively, Diaphanous and Ena drive filopodial phagocytosis to reach out and draw in debris. Macrophages switch to "filopodial phagocytosis" to overcome spatial constraint, providing the robust plasticity necessary to ensure that whatever obstacle they encounter in vivo, they fulfil their critical clearance function.