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疟疾小鼠模型的全基因组肝脏转录组学分析揭示了免疫和代谢反应的紊乱。

Genome-wide liver transcriptomic profiling of a malaria mouse model reveals disturbed immune and metabolic responses.

机构信息

Department of Medical Bioinformatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.

Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.

出版信息

Parasit Vectors. 2023 Jan 30;16(1):40. doi: 10.1186/s13071-023-05672-w.

DOI:10.1186/s13071-023-05672-w
PMID:36717945
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9885691/
Abstract

BACKGROUND

The liver is responsible for a range of functions in vertebrates, such as metabolism and immunity. In malaria, the liver plays a crucial role in the interaction between the parasite and host. Although malarial hepatitis is a common clinical complication of severe malaria, other malaria-related liver changes have been overlooked during the blood stage of the parasite life-cycle, in contrast to the many studies that have focused on parasite invasion of and replication in the liver during the hepatic stage of the parasite.

METHODS

A rodent model of malaria was established using Plasmodium yoelii strain 17XL, a lethal strain of rodent malaria, for liver transcriptomic profiling.

RESULTS

Differentially expressed messenger RNAs were associated with innate and adaptive immune responses, while differentially expressed long noncoding RNAs were enriched in the regulation of metabolism-related pathways, such as lipid metabolism. The coexpression network showed that host genes were related to cellular transport and tissue remodeling. Hub gene analysis of P. yoelii indicated that ubiquitination genes that were coexpressed with the host were evolutionarily conserved.

CONCLUSIONS

Our analysis yielded evidence of activated immune responses, aberrant metabolic processes and tissue remodeling changes in the livers of mice with malaria during the blood stage of the parasite, which provided a systematic outline of liver responses during Plasmodium infection.

摘要

背景

肝脏在脊椎动物中负责多种功能,如代谢和免疫。在疟疾中,肝脏在寄生虫和宿主之间的相互作用中起着至关重要的作用。虽然肝性疟疾是严重疟疾的常见临床并发症,但在寄生虫生活史的血液阶段,其他与疟疾相关的肝脏变化被忽视了,而许多研究都集中在寄生虫在肝期对肝脏的入侵和复制上。

方法

使用 Plasmodium yoelii 株 17XL 建立了一种疟疾啮齿动物模型,这是一种致命的啮齿动物疟疾株,用于肝脏转录组谱分析。

结果

差异表达的信使 RNA 与先天和适应性免疫反应有关,而差异表达的长非编码 RNA 则富集在代谢相关途径的调节中,如脂质代谢。共表达网络显示宿主基因与细胞运输和组织重塑有关。疟原虫的枢纽基因分析表明,与宿主共表达的泛素化基因在进化上是保守的。

结论

我们的分析表明,在寄生虫的血液阶段,感染疟原虫的小鼠肝脏中存在激活的免疫反应、异常的代谢过程和组织重塑变化,为疟原虫感染期间肝脏反应提供了系统的概述。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eae/9885691/3c88a3165ee2/13071_2023_5672_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eae/9885691/bbdb6e937ad9/13071_2023_5672_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eae/9885691/3c88a3165ee2/13071_2023_5672_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eae/9885691/bbdb6e937ad9/13071_2023_5672_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eae/9885691/9c2548ffd936/13071_2023_5672_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eae/9885691/e09c92ba9fa4/13071_2023_5672_Fig3_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eae/9885691/3c88a3165ee2/13071_2023_5672_Fig5_HTML.jpg

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Acute Kidney Injury Interacts With Coma, Acidosis, and Impaired Perfusion to Significantly Increase Risk of Death in Children With Severe Malaria.
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