Capsular polysaccharides from Cryptococcus neoformans modulate production of neutrophil extracellular traps (NETs) by human neutrophils.
Capsular polysaccharides from Cryptococcus neoformans modulate production of neutrophil extracellular traps (NETs) by human neutrophils.
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DOI：
10.1038/srep08008
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发表时间：
2015-01-26
影响因子：
4.6
通讯作者：
Freire-de-Lima CG
中科院分区：
文献类型：
--
作者：
Rocha JD;Nascimento MT;Decote-Ricardo D;Côrte-Real S;Morrot A;Heise N;Nunes MP;Previato JO;Mendonça-Previato L;DosReis GA;Saraiva EM;Freire-de-Lima CG
在本研究中，我们描述了机会性真菌新生隐球菌在人中性粒细胞中诱导的NET（中性粒细胞胞外陷阱）的体外调节，评估了荚膜多糖葡糖醛酸木甘聚糖（GXM）和葡糖醛酸木甘露半乳聚糖（GXMGal）在这种现象中的参与。突变型无荚膜菌株 CAP67 和荚膜多糖 GXMGal 诱导 NET 产生。相反，野生型菌株和主要多糖GXM不诱导NET释放。此外，新型隐球菌和荚膜多糖 GXM 抑制 PMA 诱导的 NET 释放。此外，我们观察到通过CAP67酵母诱导的富含NET的上清液对荚膜菌株表现出杀菌活性，并且中性粒细胞弹性蛋白酶、髓过氧化物酶、胶原酶和组蛋白是诱导NET杀菌活性的关键成分。 CAP67 菌株与 NET 诱导相关的信号通路依赖于活性氧 (ROS) 和肽基精氨酸脱亚胺酶 4 (PAD-4)。两种多糖均不诱导 ROS 产生，但两种分子均通过 PMA 激活的中性粒细胞阻断 ROS 的产生。综上所述，结果表明新型隐球菌和荚膜成分 GXM 抑制人中性粒细胞中 NET 的产生。这种机制表明这种真菌病原体有一个潜在的新的重要调节因子。
In the present study, we characterized the in vitro modulation of NETs (neutrophil extracellular traps) induced in human neutrophils by the opportunistic fungus Cryptococcus neoformans, evaluating the participation of capsular polysaccharides glucuronoxylomanan (GXM) and glucuronoxylomannogalactan (GXMGal) in this phenomenon. The mutant acapsular strain CAP67 and the capsular polysaccharide GXMGal induced NET production. In contrast, the wild-type strain and the major polysaccharide GXM did not induce NET release. In addition, C. neoformans and the capsular polysaccharide GXM inhibited PMA-induced NET release. Additionally, we observed that the NET-enriched supernatants induced through CAP67 yeasts showed fungicidal activity on the capsular strain, and neutrophil elastase, myeloperoxidase, collagenase and histones were the key components for the induction of NET fungicidal activity. The signaling pathways associated with NET induction through the CAP67 strain were dependent on reactive oxygen species (ROS) and peptidylarginine deiminase-4 (PAD-4). Neither polysaccharide induced ROS production however both molecules blocked the production of ROS through PMA-activated neutrophils. Taken together, the results demonstrate that C. neoformans and the capsular component GXM inhibit the production of NETs in human neutrophils. This mechanism indicates a potentially new and important modulation factor for this fungal pathogen.
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影响因子：
6.7
作者：
Bruns S;Kniemeyer O;Hasenberg M;Aimanianda V;Nietzsche S;Thywissen A;Jeron A;Latgé JP;Brakhage AA;Gunzer M
通讯作者：
Gunzer M
DOI：
10.1084/jem.20100239
发表时间：
2010-08-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Li P;Li M;Lindberg MR;Kennett MJ;Xiong N;Wang Y
通讯作者：
Wang Y
DOI：
10.1038/nrrheum.2011.132
发表时间：
2011-09-27
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.7
作者：
Hemmers S;Teijaro JR;Arandjelovic S;Mowen KA
通讯作者：
Mowen KA
影响因子：
4.6
作者：
Kirchner T;Möller S;Klinger M;Solbach W;Laskay T;Behnen M
通讯作者：
Behnen M