Mechanisms involved in the triggering of neutrophil extracellular traps (NETs) by Candida glabrata during planktonic and biofilm growth.
Mechanisms involved in the triggering of neutrophil extracellular traps (NETs) by Candida glabrata during planktonic and biofilm growth.
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DOI：
10.1038/s41598-017-13588-6
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发表时间：
2017-10-12
影响因子：
4.6
通讯作者：
Nett JE
中科院分区：
文献类型：
--
作者：
Johnson CJ;Kernien JF;Hoyer AR;Nett JE
念珠菌粘附在医疗器械上，如导管，形成耐药性生物膜，抵抗免疫系统的杀伤。很少有人知道C。glabrata是一种新出现的病原体，可抵抗吞噬细胞的攻击。在这里，我们表明，在遇到嗜酸性（非生物膜）C。在glabrata中，人嗜中性粒细胞最初吞噬酵母，随后释放嗜中性粒细胞胞外陷阱（NET），DNA、组蛋白和能够抑制真菌生长和传播的蛋白质的复合物。当暴露于C.在glabrata生物膜中，嗜中性粒细胞也释放NET，但显著少于响应于无张力细胞。生物膜的杀伤受损与NET产量的减少平行。与生物膜相比，中性粒细胞在与嗜酸性生物接触时产生更高水平的活性氧（ROS），NADPH氧化酶的药理学抑制部分损害NET的产生。相反，抑制吞噬作用几乎完全阻断NET释放到生物膜和浮游生物。宿主对C. glabrata在大鼠血管感染模型中的作用支持NET在体内释放的作用。综上所述，这些研究结果表明，C。glabrata触发NET释放。NET对C.光滑的生物膜可能有助于这些结构化群落对宿主防御的恢复力。
Candida spp. adhere to medical devices, such as catheters, forming drug-tolerant biofilms that resist killing by the immune system. Little is known about how C. glabrata, an emerging pathogen, resists attack by phagocytes. Here we show that upon encounter with planktonic (non-biofilm) C. glabrata, human neutrophils initially phagocytose the yeast and subsequently release neutrophil extracellular traps (NETs), complexes of DNA, histones, and proteins capable of inhibiting fungal growth and dissemination. When exposed to C. glabrata biofilms, neutrophils also release NETs, but significantly fewer than in response to planktonic cells. Impaired killing of biofilm parallels the decrease in NET production. Compared to biofilm, neutrophils generate higher levels of reactive oxygen species (ROS) when presented with planktonic organisms, and pharmacologic inhibition of NADPH-oxidase partially impairs NET production. In contrast, inhibition of phagocytosis nearly completely blocks NET release to both biofilm and planktonic organisms. Imaging of the host response to C. glabrata in a rat vascular model of infection supports a role for NET release in vivo. Taken together, these findings show that C. glabrata triggers NET release. The diminished NET response to C. glabrata biofilms likely contributes to the resilience of these structured communities to host defenses.
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影响因子：
3.4
作者：
Brunke S;Hube B
通讯作者：
Hube B
影响因子：
11.8
作者：
Horn, David L.;Neofytos, Dionissios;Webster, Karen M.
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6.7
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3
作者：
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通讯作者：
Kurzai, Oliver
影响因子：
3.1
作者：
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通讯作者：
Pitula, A