Immune cells fold and damage fungal hyphae.

Immune cells fold and damage fungal hyphae.
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DOI:
10.1073/pnas.2020484118
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发表时间:
2021-04-13
影响因子:
11.1
通讯作者:
Brown AJP
Brown AJP
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Bain JM;Alonso MF;Childers DS;Walls CA;Mackenzie K;Pradhan A;Lewis LE;Louw J;Avelar GM;Larcombe DE;Netea MG;Gow NAR;Brown GD;Erwig LP;Brown AJP

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巨噬细胞通过吞噬和杀死入侵的微生物来防止微生物感染。众所周知,白色念珠菌等真菌病原体通过形成菌丝来逃避吞噬细胞的杀戮,由于它们的长度,菌丝在物理上很难吞噬。我们现在发现,巨噬细胞可以通过折叠白色念珠菌(和其他真菌物种)的菌丝来做出反应。菌丝折叠意味着免疫细胞在其货物内化后可以继续施加机械力。Dectin-1、β2-整合素和肌动蛋白-肌球蛋白聚合的参与提供了初步的机制洞察。折叠破坏菌丝,抑制其生长,并促进其完全吞噬。因此,菌丝折叠是免疫细胞库中的一种额外武器,可能有助于真菌的清除。先天免疫对威胁生命的真菌感染提供了基本的保护。然而,免疫细胞和真菌病原体之间的个别小规模冲突的结果并不是必然的结果,因为一些病原体已经进化出逃避吞噬细胞识别、吞噬和杀伤的机制。例如,白色念珠菌可以通过激活细胞形态发生来形成难以吞噬的长菌丝来逃避吞噬作用。通过对白色念珠菌-巨噬细胞相互作用的实时成像,我们发现巨噬细胞可以通过折叠真菌菌丝来抵消这种作用。真菌菌丝的折叠受Dectin-1、β2-整合素、Vasp、肌动蛋白-肌球蛋白聚合和细胞运动的促进。在某些情况下,折叠有助于完全吞噬长菌丝,并抑制菌丝生长,可能会使平衡朝着成功的真菌清除倾斜。
Macrophages protect against microbial infection, in part by engulfing and killing invading microbes. Fungal pathogens such as Candida albicans are known to evade phagocytic killing by forming hyphae that are physically challenging to engulf because of their length. We now find that macrophages can respond by folding the hyphae of C. albicans (and other fungal species). Hyphal folding implies that immune cells can continue to apply mechanical force after their cargo has been internalized. The involvement of Dectin-1, β2-integrin, and actin–myosin polymerization provides initial mechanistic insight. Folding damages hyphae, inhibits their growth, and facilitates their complete engulfment. Therefore, hyphal folding represents an additional weapon in the immune cell armory that presumably contributes to fungal clearance. Innate immunity provides essential protection against life-threatening fungal infections. However, the outcomes of individual skirmishes between immune cells and fungal pathogens are not a foregone conclusion because some pathogens have evolved mechanisms to evade phagocytic recognition, engulfment, and killing. For example, Candida albicans can escape phagocytosis by activating cellular morphogenesis to form lengthy hyphae that are challenging to engulf. Through live imaging of C. albicans–macrophage interactions, we discovered that macrophages can counteract this by folding fungal hyphae. The folding of fungal hyphae is promoted by Dectin-1, β2-integrin, VASP, actin–myosin polymerization, and cell motility. Folding facilitates the complete engulfment of long hyphae in some cases and it inhibits hyphal growth, presumably tipping the balance toward successful fungal clearance.
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