Mucosal candidiasis elicits NF-κB activation, proinflammatory gene expression and localized neutrophilia in zebrafish.
Mucosal candidiasis elicits NF-κB activation, proinflammatory gene expression and localized neutrophilia in zebrafish.
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DOI：
10.1242/dmm.012039
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发表时间：
2013-09
影响因子：
4.3
通讯作者：
Wheeler RT
中科院分区：
文献类型：
--
作者：
Gratacap RL;Rawls JF;Wheeler RT
上皮在动物与其环境之间的界面处执行平衡作用，以使病原体杀灭和肠道微生物的耐受性两者成为可能。白色念珠菌是临床上重要的人类真菌，其定殖于所有人类粘膜表面，但在免疫活性个体中很大程度上防止引起粘膜感染。尽管了解宿主-病原体在上皮的相互作用的重要性，没有免疫活性脊椎动物模型已被用于可视化这些动态非侵入性。在这里，我们证明了重要的相似之处在透明的斑马鱼和粘膜感染的哺乳动物上皮的鳔念珠菌病。具体来说，在斑马鱼的游泳膀胱感染模型中，我们发现了双相真菌生长，局部和组织范围的上皮NF-κB激活，NF-κB依赖性促炎基因的诱导，以及强烈的嗜中性粒细胞。与主要基于组织培养实验的宿主反应的密度依赖性模型一致，我们表明，只有高水平感染才能引起上皮细胞中NF-κB的广泛激活和促炎基因的诱导。与使用体外哺乳动物模型所发现的相似，我们发现上皮NF-κB活化可以发生在与上皮细胞直接接触的距离处。利用高分辨率非侵入性成像感染和宿主信号传导的能力，我们还报告了当吞噬细胞控制感染时，上皮NF-κB活化减少。这是第一个模拟宿主对幼年斑马鱼粘膜感染反应的系统，并提供了独特的机会来研究C。白色念珠菌、上皮细胞和免疫细胞。
The epithelium performs a balancing act at the interface between an animal and its environment to enable both pathogen killing and tolerance of commensal microorganisms. Candida albicans is a clinically important human commensal that colonizes all human mucosal surfaces, yet is largely prevented from causing mucosal infections in immunocompetent individuals. Despite the importance of understanding host-pathogen interactions at the epithelium, no immunocompetent vertebrate model has been used to visualize these dynamics non-invasively. Here we demonstrate important similarities between swimbladder candidiasis in the transparent zebrafish and mucosal infection at the mammalian epithelium. Specifically, in the zebrafish swimmbladder infection model, we show dimorphic fungal growth, both localized and tissue-wide epithelial NF-κB activation, induction of NF-κB -dependent proinflammatory genes, and strong neutrophilia. Consistent with density-dependence models of host response based primarily on tissue culture experiments, we show that only high-level infection provokes widespread activation of NF-κB in epithelial cells and induction of proinflammatory genes. Similar to what has been found using in vitro mammalian models, we find that epithelial NF-κB activation can occur at a distance from the immediate site of contact with epithelial cells. Taking advantage of the ability to non-invasively image infection and host signaling at high resolution, we also report that epithelial NF-κB activation is diminished when phagocytes control the infection. This is the first system to model host response to mucosal infection in the juvenile zebrafish, and offers unique opportunities to investigate the tripartite interactions of C. albicans, epithelium and immune cells in an intact host.
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DOI：
10.4049/jimmunol.1100500
发表时间：
2011-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ather JL;Ckless K;Martin R;Foley KL;Suratt BT;Boyson JE;Fitzgerald KA;Flavell RA;Eisenbarth SC;Poynter ME
通讯作者：
Poynter ME
DOI：
10.1016/j.bbrc.2010.08.037
发表时间：
2010-09-10
影响因子：
3.1
作者：
Flores, Maria Vega;Crawford, Katie C.;Crosier, Philip S.
通讯作者：
Crosier, Philip S.
影响因子：
--
作者：
Brothers, Kimberly M.;Newman, Zachary R.;Wheeler, Robert T.
通讯作者：
Wheeler, Robert T.
影响因子：
2.6
作者：
GIETZ, RD;SCHIESTL, RH;WOODS, RA
通讯作者：
WOODS, RA
影响因子：
3.1
作者：
Fidel, PL;Barousse, M;Dunlap, K
通讯作者：
Dunlap, K