Cordycepin, a metabolite of Cordyceps militaris, reduces immune-related gene expression in insects.

Cordycepin, a metabolite of Cordyceps militaris, reduces immune-related gene expression in insects.
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DOI:
10.1016/j.jip.2020.107480
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发表时间:
2020-11
影响因子:
3.4
通讯作者:
Chandler D
Chandler D
中科院分区:
生物学3区
文献类型:
--
作者:
Woolley VC;Teakle GR;Prince G;de Moor CH;Chandler D

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高剂量虫草素对G.梅隆内拉虫草素与EPF相互作用可提高G.大蜡螟死亡率虫草素降低G. Mellonella和S2 r+细胞。肉座菌纲昆虫病原真菌(EPF)(球壳菌纲,子囊菌门)是陆地环境中昆虫种群的天然调节因子。它们专杀性的生命周期意味着它们可能有强大的选择压力,使它们能够逃避宿主免疫系统的影响。本研究以蛹虫草(Cordyceps militaris,Hypocreales,Cordycipitaceae)为研究对象,研究蛹虫草(Cordyceps militaris,Hypocreales)次级代谢产物虫草素(Cordycepin,3′-deoxyadenosine)对昆虫EPF感染敏感性和昆虫免疫基因表达的影响。将免疫刺激剂凝胶多糖(20 µg ml−1,线性β-1,3-葡聚糖,真菌细胞壁的一种成分)应用于果蝇S2 r+细胞,与仅使用DMSO的对照相比,免疫效应基因metchnikowin的表达显著增加,但当凝胶多糖与25 µg ml−1溶于DMSO的虫草素共同应用时,没有显著增加。将虫草素注射到大蜡螟(鳞翅目:螟蛾科)幼虫中导致剂量依赖性死亡率(处理后6天,虫草素的LC 50 = 2.1 mg/昆虫)。孢子孵化。蛹孢和球孢白僵菌(肉座菌目,虫草科;一种不合成虫草素的EPF)与3.0 mg ml−1虫草素在体外对孢子萌发的数量没有影响。共注射G.用低浓度的虫草素(3.0 mg ml-1)加上每只昆虫10或100个分生孢子的C. militaris或B.与单独注射EPF相比,接种球孢白僵菌引起昆虫中位存活时间的显著降低。预测与观察到的死亡率的分析表明虫草素和EPF之间的协同相互作用。C. militaris和B. bassiana转化为G.在注射后72小时,大蜡螟导致昆虫免疫效应基因溶菌酶、IMPI和盖勒霉素的表达增加,但当EPF与3.0 mg ml−1虫草素共注射时,这并不发生。此外,我们观察到IMPI和溶菌酶在注射C.军事,B。bassiana和假注射(表明创伤反应),但这也被应用虫草素阻止。这些结果表明,虫草素有可能作为一种抑制剂的免疫反应,在真菌感染的昆虫宿主。
High doses of cordycepin are lethal to G. mellonella. Cordycepin interacts with EPF to increase the rate of G. mellonella mortality. Cordycepin reduces immune-related gene expression in G. mellonella and S2r+ cells. Hypocrealean entomopathogenic fungi (EPF) (Sordariomycetes, Ascomycota) are natural regulators of insect populations in terrestrial environments. Their obligately-killing life-cycle means that there is likely to be strong selection pressure for traits that allow them to evade the effects of the host immune system. In this study, we quantified the effects of cordycepin (3′-deoxyadenosine), a secondary metabolite produced by Cordyceps militaris (Hypocreales, Cordycipitaceae), on insect susceptibility to EPF infection and on insect immune gene expression. Application of the immune stimulant curdlan (20 µg ml−1, linear beta-1,3-glucan, a constituent of fungal cell walls) to Drosophila melanogaster S2r+ cells resulted in a significant increase in the expression of the immune effector gene metchnikowin compared to a DMSO-only control, but there was no significant increase when curdlan was co-applied with 25 µg ml−1 cordycepin dissolved in DMSO. Injection of cordycepin into larvae of Galleria mellonella (Lepidoptera: Pyralidae) resulted in dose-dependent mortality (LC50 of cordycepin = 2.1 mg per insect 6 days after treatment). Incubating conidia of C. militaris and Beauveria bassiana (Hypocreales, Cordycipitaceae; an EPF that does not synthesize cordycepin) with 3.0 mg ml−1 cordycepin had no effect on the numbers of conidia germinating in vitro. Co-injection of G. mellonella with a low concentration of cordycepin (3.0 mg ml−1) plus 10 or 100 conidia per insect of C. militaris or B. bassiana caused a significant decrease in insect median survival time compared to injection with the EPF on their own. Analysis of predicted vs. observed mortalities indicated a synergistic interaction between cordycepin and the EPF. The injection of C. militaris and B. bassiana into G. mellonella resulted in increased expression of the insect immune effector genes lysozyme, IMPI and gallerimycin at 72 h post injection, but this did not occur when the EPF were co-injected with 3.0 mg ml−1 cordycepin. In addition, we observed increased expression of IMPI and lysozyme at 48 h after injection with C. militaris, B. bassiana and sham injection (indicating a wounding response), but this was also prevented by application of cordycepin. These results suggest that cordycepin has potential to act as a suppressor of the immune response during fungal infection of insect hosts.
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