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转化生长因子-β信号传导干扰对寄生线虫感染的固有免疫和代谢反应。

TGF-β Signaling Interferes With the Innate Immune and Metabolic Response to Parasitic Nematode Infection.

作者信息

Ozakman Yaprak, Eleftherianos Ioannis

机构信息

Infection and Innate Immunity Laboratory, Department of Biological Sciences, The George Washington University, Washington, DC, United States.

出版信息

Front Physiol. 2019 Jun 19;10:716. doi: 10.3389/fphys.2019.00716. eCollection 2019.

Abstract

The common fruit fly, , is an outstanding model to study the molecular basis of anti-pathogen immunity. The parasitic nematode together with its mutualistic bacteria infects a wide range of insects, including . Recently, we have shown that transforming growth factor-β (TGF-ß) signaling in is regulated in response to parasitic nematode infection. In the current study, we investigated the contribution of two TGF-ß signaling branches, the activin and the bone morphogenetic protein (BMP), to immune function against . We used larvae carrying mutations in the genes coding for the TGF-ß extracellular ligands and . We have demonstrated that the number of circulating hemocytes in uninfected and mutants decreases twofold compared to background controls, yet no significant changes in hemocyte numbers and survival of the TGF-ß mutants are observed upon nematode infection. However, we have shown that nematode-infected mutants express at higher levels and phenoloxidase activity at lower levels compared to their background controls. To elucidate the contribution of TGF-ß signaling in the metabolic response of to parasitic nematodes, we estimated lipid and carbohydrate levels in and mutant larvae infected with . We have found that both nematode-infected mutants contain lipid droplets of larger size, with mutant larvae also containing elevated glycogen levels. Overall, our findings indicate that the regulation of activin and BMP branches of TGF-ß signaling can alter the immune and metabolic processes in during response to parasitic nematode infection. Results from this study shed light on the molecular signaling pathways insects activate to regulate mechanisms for fighting potent nematode parasites, which could lead to the identification of novel management strategies for the control of damaging pests.

摘要

普通果蝇是研究抗病原体免疫分子基础的杰出模型。寄生线虫及其共生细菌会感染包括果蝇在内的多种昆虫。最近,我们发现果蝇体内的转化生长因子-β(TGF-β)信号通路会因寄生线虫感染而受到调控。在本研究中,我们调查了TGF-β信号通路的两个分支——激活素和骨形态发生蛋白(BMP)对果蝇抵抗寄生线虫免疫功能的贡献。我们使用了编码TGF-β细胞外配体的基因发生突变的果蝇幼虫。我们已经证明,与背景对照相比,未感染的果蝇和突变体中循环血细胞的数量减少了两倍,但在感染线虫后,未观察到TGF-β突变体的血细胞数量和存活率有显著变化。然而,我们发现,与背景对照相比,感染线虫的突变体表达水平更高,酚氧化酶活性更低。为了阐明TGF-β信号通路在果蝇对寄生线虫代谢反应中的作用,我们估计了感染寄生线虫的果蝇和突变体幼虫中的脂质和碳水化合物水平。我们发现,两种感染线虫的突变体都含有更大尺寸的脂滴,突变体幼虫的糖原水平也有所升高。总体而言,我们的研究结果表明,TGF-β信号通路的激活素和BMP分支的调控可以改变果蝇在应对寄生线虫感染时的免疫和代谢过程。这项研究的结果揭示了昆虫激活的分子信号通路,以调节对抗强大线虫寄生虫的机制,这可能有助于识别控制有害害虫的新管理策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef69/6611403/4048a14420fc/fphys-10-00716-g001.jpg

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