Parasitoid wasp venom SERCA regulates Drosophila calcium levels and inhibits cellular immunity
Parasitoid wasp venom SERCA regulates Drosophila calcium levels and inhibits cellular immunity
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DOI：
10.1073/pnas.1222351110
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发表时间：
2013-06-04
影响因子：
11.1
通讯作者：
Schlenke, Todd A.
中科院分区：
文献类型：
--
作者：
Mortimer, Nathan T.;Goecks, Jeremy;Schlenke, Todd A.
由于寄生虫毒力因子以宿主免疫反应为靶标，对这些因子的鉴定和功能表征可以帮助我们深入了解尚不清楚的宿主免疫机制。果蝇是理解体液天然免疫的模型系统，但果蝇的细胞天然免疫反应仍未完全确定。果蝇在自然界中经常被寄生蜂感染，感染后，果蝇会启动细胞免疫反应，最终导致黄蜂卵的细胞包裹。这种反应的机制基础在很大程度上尚不清楚，但黄蜂使用来自毒腺的毒力蛋白混合物来抑制细胞包裹。为了深入了解黄蜂毒力和苍蝇细胞免疫的机制，我们使用联合转录/蛋白质组学方法鉴定了果蝇寄生蜂Ganaspis sp.1(G1)的毒液基因，发现G1毒液含有高度丰富的肌浆/内质网钙ATPase(SERCA)泵。因此，我们发现被称为浆细胞的苍蝇免疫细胞通常在感染后经历细胞质钙爆发，而这种钙爆发是激活细胞免疫反应所必需的。我们进一步发现，G1毒液以一种SERCA依赖的方式抑制浆细胞钙爆发，导致浆细胞无法激活并向G1卵迁移。最后，通过遗传操作浆细胞钙水平，我们能够改变苍蝇对G1和其他寄生蜂物种的免疫成功。我们对寄生蜂毒液蛋白的表征使我们确定浆细胞胞质钙爆发是苍蝇细胞免疫的一个重要方面。
Because parasite virulence factors target host immune responses, identification and functional characterization of these factors can provide insight into poorly understood host immune mechanisms. The fruit fly Drosophila melanogaster is a model system for understanding humoral innate immunity, but Drosophila cellular innate immune responses remain incompletely characterized. Fruit flies are regularly infected by parasitoid wasps in nature and, following infection, flies mount a cellular immune response culminating in the cellular encapsulation of the wasp egg. The mechanistic basis of this response is largely unknown, but wasps use a mixture of virulence proteins derived from the venom gland to suppress cellular encapsulation. To gain insight into the mechanisms underlying wasp virulence and fly cellular immunity, we used a joint transcriptomic/proteomic approach to identify venom genes from Ganaspis sp.1 (G1), a previously uncharacterized Drosophila parasitoid species, and found that G1 venom contains a highly abundant sarco/endoplasmic reticulum calcium ATPase (SERCA) pump. Accordingly, we found that fly immune cells termed plasmatocytes normally undergo a cytoplasmic calcium burst following infection, and that this calcium burst is required for activation of the cellular immune response. We further found that the plasmatocyte calcium burst is suppressed by G1 venom in a SERCA-dependent manner, leading to the failure of plasmatocytes to become activated and migrate toward G1 eggs. Finally, by genetically manipulating plasmatocyte calcium levels, we were able to alter fly immune success against G1 and other parasitoid species. Our characterization of parasitoid wasp venom proteins led us to identify plasmatocyte cytoplasmic calcium bursts as an important aspect of fly cellular immunity.