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利什曼原虫诱导的宿主细胞和全身铜稳态改变决定了感染的命运。

Leishmania major-induced alteration of host cellular and systemic copper homeostasis drives the fate of infection.

机构信息

Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, West Bengal, India.

Department of Chemistry, University of California Berkeley, Berkeley, CA, USA.

出版信息

Commun Biol. 2024 Sep 30;7(1):1226. doi: 10.1038/s42003-024-06716-2.

DOI:10.1038/s42003-024-06716-2
PMID:39349621
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11442737/
Abstract

Copper plays a key role in host-pathogen interaction. We find that during Leishmania major infection, the parasite-harboring macrophage regulates its copper homeostasis pathway in a way to facilitate copper-mediated neutralization of the pathogen. Copper-ATPase ATP7A transports copper to amastigote-harboring phagolysosomes to induce stress on parasites. Leishmania in order to evade the copper stress, utilizes a variety of manipulative measures to lower the host-induced copper stress. It induces deglycosylation and degradation of host-ATP7A and downregulation of copper importer, CTR1 by cysteine oxidation. Additionally, Leishmania induces CTR1 endocytosis that arrests copper uptake. In mouse model of infection, we report an increase in systemic bioavailable copper in infected animals. Heart acts as the major organ for diverting its copper reserves to systemic circulation to fight-off infection by downregulating its CTR1. Our study explores reciprocal mechanism of manipulation of host copper homeostasis pathway by macrophage and Leishmania to gain respective advantages in host-pathogen interaction.

摘要

铜在宿主-病原体相互作用中起着关键作用。我们发现，在感染利什曼原虫时，寄生虫携带的巨噬细胞会调节其铜稳态途径，以促进铜介导的病原体中和。铜-ATP 酶 ATP7A 将铜转运到含利什曼原虫的吞噬溶酶体中，以诱导寄生虫产生应激。为了逃避铜应激，利什曼原虫利用多种操纵措施降低宿主诱导的铜应激。它诱导宿主 ATP7A 的去糖基化和降解，并通过半胱氨酸氧化下调铜摄取体 CTR1。此外，利什曼原虫诱导 CTR1 内吞作用，从而阻止铜摄取。在感染的小鼠模型中，我们报告感染动物体内系统生物可利用铜增加。心脏作为主要器官，通过下调其 CTR1 将其铜储备转移到全身循环，以抵御感染。我们的研究探索了巨噬细胞和利什曼原虫对宿主铜稳态途径的相互操纵机制，以在宿主-病原体相互作用中获得各自的优势。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/281c/11442737/e0234ea5485b/42003_2024_6716_Fig1_HTML.jpg
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本文引用的文献

1
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Proc Natl Acad Sci U S A. 2024 Jan 23;121(4):e2311630121. doi: 10.1073/pnas.2311630121. Epub 2024 Jan 17.
2
Copper(II) import and reduction are dependent on His-Met clusters in the extracellular amino terminus of human copper transporter-1.铜（II）的摄取和还原依赖于人铜转运蛋白-1胞外氨基末端的 His-Met 簇。
J Biol Chem. 2022 Mar;298(3):101631. doi: 10.1016/j.jbc.2022.101631. Epub 2022 Jan 26.
3
Cysteine oxidation of copper transporter CTR1 drives VEGFR2 signalling and angiogenesis.
半胱氨酸氧化的铜转运蛋白 CTR1 驱动 VEGFR2 信号转导和血管生成。
Nat Cell Biol. 2022 Jan;24(1):35-50. doi: 10.1038/s41556-021-00822-7. Epub 2022 Jan 13.
4
A novel leishmanial copper P-type ATPase plays a vital role in parasite infection and intracellular survival.一种新型利什曼原虫铜 P 型 ATP 酶在寄生虫感染和细胞内生存中起着至关重要的作用。
J Biol Chem. 2022 Feb;298(2):101539. doi: 10.1016/j.jbc.2021.101539. Epub 2021 Dec 25.
5
Copper detoxification machinery of the brain-eating amoeba Naegleria fowleri involves copper-translocating ATPase and the antioxidant system.食脑变形虫（Naegleria fowleri）的脑部铜解毒机制涉及铜转运 ATP 酶和抗氧化系统。
Int J Parasitol Drugs Drug Resist. 2020 Dec;14:126-135. doi: 10.1016/j.ijpddr.2020.10.001. Epub 2020 Oct 7.
6
Inhibition of N-linked Glycosylation by Tunicamycin May Contribute to The Treatment of SARS-CoV-2.衣霉素抑制 N-连接糖基化可能有助于治疗 SARS-CoV-2。
Microb Pathog. 2020 Dec;149:104586. doi: 10.1016/j.micpath.2020.104586. Epub 2020 Oct 20.
7
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Lancet. 2018 Sep 15;392(10151):951-970. doi: 10.1016/S0140-6736(18)31204-2. Epub 2018 Aug 17.
8
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9
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10
Host Cell Copper Transporters CTR1 and ATP7A are important for Influenza A virus replication.宿主细胞铜转运蛋白CTR1和ATP7A对甲型流感病毒复制很重要。
Virol J. 2017 Jan 23;14(1):11. doi: 10.1186/s12985-016-0671-7.