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含硫酯蛋白调控 Toll 通路,并在果蝇抵御微生物病原体和寄生蜂方面发挥作用。

Thioester-containing proteins regulate the Toll pathway and play a role in Drosophila defence against microbial pathogens and parasitoid wasps.

机构信息

Global Health Institute, School of Life Sciences, École Polytechnique Fédérale Lausanne (EPFL), CH-1015, Lausanne, Switzerland.

Institute for Integrative Biology of the Cell, Université Paris-Saclay, CEA, CNRS, Université Paris Sud, 1 Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.

出版信息

BMC Biol. 2017 Sep 5;15(1):79. doi: 10.1186/s12915-017-0408-0.

Abstract

BACKGROUND

Members of the thioester-containing protein (TEP) family contribute to host defence in both insects and mammals. However, their role in the immune response of Drosophila is elusive. In this study, we address the role of TEPs in Drosophila immunity by generating a mutant fly line, referred to as TEPq , lacking the four immune-inducible TEPs, TEP1, 2, 3 and 4.

RESULTS

Survival analyses with TEPq flies reveal the importance of these proteins in defence against entomopathogenic fungi, Gram-positive bacteria and parasitoid wasps. Our results confirm that TEPs are required for efficient phagocytosis of bacteria, notably for the two Gram-positive species tested, Staphylococcus aureus and Enterococcus faecalis. Furthermore, we show that TEPq flies have reduced Toll pathway activation upon microbial infection, resulting in lower expression of antimicrobial peptide genes. Epistatic analyses suggest that TEPs function upstream or independently of the serine protease ModSP at an initial stage of Toll pathway activation.

CONCLUSIONS

Collectively, our study brings new insights into the role of TEPs in insect immunity. It reveals that TEPs participate in both humoral and cellular arms of immune response in Drosophila. In particular, it shows the importance of TEPs in defence against Gram-positive bacteria and entomopathogenic fungi, notably by promoting Toll pathway activation.

摘要

背景

含硫酯蛋白 (TEP) 家族的成员为昆虫和哺乳动物的宿主防御做出了贡献。然而,它们在果蝇免疫反应中的作用尚不清楚。在这项研究中,我们通过生成一个突变果蝇系,称为 TEPq ,缺乏四个免疫诱导的 TEPs(TEP1、2、3 和 4),来研究 TEPs 在果蝇免疫中的作用。

结果

对 TEPq 果蝇的生存分析表明,这些蛋白质在防御昆虫病原真菌、革兰氏阳性菌和寄生蜂方面具有重要作用。我们的结果证实,TEPs 是有效吞噬细菌所必需的,特别是针对测试的两种革兰氏阳性菌金黄色葡萄球菌和粪肠球菌。此外,我们表明,TEPq 果蝇在微生物感染后 Toll 途径的激活减少,导致抗菌肽基因的表达降低。上位性分析表明,TEPs 在 Toll 途径激活的初始阶段,在上游或独立于丝氨酸蛋白酶 ModSP 发挥作用。

结论

总的来说,我们的研究为 TEPs 在昆虫免疫中的作用提供了新的见解。它表明 TEPs 参与了果蝇免疫的体液和细胞免疫反应。特别是,它表明 TEPs 在防御革兰氏阳性菌和昆虫病原真菌方面的重要性,特别是通过促进 Toll 途径的激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9faa/5584532/181cd95ab227/12915_2017_408_Fig1_HTML.jpg

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