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Plasma membrane abundance dictates phagocytic capacity and functional cross-talk in myeloid cells
Science Immunology ( IF 17.6 ) Pub Date : 2024-06-07 , DOI: 10.1126/sciimmunol.adl2388
Benjamin Y Winer 1, 2, 3, 4 , Alexander H Settle 1 , Alexandrina M Yakimov 1 , Carlos Jeronimo 1 , Tomi Lazarov 1 , Murray Tipping 5 , Michelle Saoi 6 , Anjelique Sawh 7 , Anna-Liisa L Sepp 8 , Michael Galiano 5 , Justin S A Perry 1 , Yung Yu Wong 1 , Frederic Geissmann 1 , Justin Cross 6 , Ting Zhou 9, 10 , Lance C Kam 8 , H Amalia Pasolli 11 , Tobias Hohl 12 , Jason G Cyster 2, 13 , Orion D Weiner 3, 4 , Morgan Huse 1
Affiliation  

Professional phagocytes like neutrophils and macrophages tightly control what they consume, how much they consume, and when they move after cargo uptake. We show that plasma membrane abundance is a key arbiter of these cellular behaviors. Neutrophils and macrophages lacking the G protein subunit Gβ 4 exhibited profound plasma membrane expansion, accompanied by marked reduction in plasma membrane tension. These biophysical changes promoted the phagocytosis of bacteria, fungus, apoptotic corpses, and cancer cells. We also found that Gβ 4 -deficient neutrophils are defective in the normal inhibition of migration following cargo uptake. Sphingolipid synthesis played a central role in these phenotypes by driving plasma membrane accumulation in cells lacking Gβ 4 . In Gβ 4 knockout mice, neutrophils not only exhibited enhanced phagocytosis of inhaled fungal conidia in the lung but also increased trafficking of engulfed pathogens to other organs. Together, these results reveal an unexpected, biophysical control mechanism central to myeloid functional decision-making.

中文翻译:


质膜丰度决定骨髓细胞的吞噬能力和功能串扰



中性粒细胞和巨噬细胞等专业吞噬细胞严格控制它们消耗的内容、消耗的量以及它们在摄取货物后何时移动。我们证明质膜丰度是这些细胞行为的关键仲裁者。缺乏 G 蛋白亚基 Gβ 的中性粒细胞和巨噬细胞4表现出严重的质膜扩张,同时质膜张力显着降低。这些生物物理变化促进了细菌、真菌、凋亡尸体和癌细胞的吞噬作用。我们还发现Gβ 4 -缺乏的中性粒细胞在吸收货物后的正常迁移抑制方面存在缺陷。鞘脂合成通过驱动缺乏 Gβ 的细胞质膜积累而在这些表型中发挥核心作用4 。在Gβ中4在基因敲除小鼠中,中性粒细胞不仅表现出对肺部吸入的真菌分生孢子的吞噬能力增强,而且还增加了吞噬病原体向其他器官的运输。总之,这些结果揭示了一种意想不到的生物物理控制机制,对于骨髓功能决策至关重要。
更新日期:2024-06-07
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