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与急性致死性肺炎发病机制潜在相关的肺固有免疫反应的转录组分析

Transcriptome Profiling of Lung Innate Immune Responses Potentially Associated With the Pathogenesis of Acute Lethal Pneumonia.

作者信息

Zeng Xi, Gu Hao, Peng Liusheng, Yang Yao, Wang Ning, Shi Yun, Zou Quanming

机构信息

Department of Microbiology and Biochemical Pharmacy, National Engineering Research Center of Immunological Products, College of Pharmacy, Army Medical University, Chongqing, China.

Institute of Biopharmaceutical Research, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Front Immunol. 2020 Apr 22;11:708. doi: 10.3389/fimmu.2020.00708. eCollection 2020.

DOI:10.3389/fimmu.2020.00708
PMID:32391015
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7188829/
Abstract

is one of the dominating causes of nosocomial pneumonia, however, very little is known about the host immune response associated with pathogenesis of infection. Here, we used a hypervirulent to establish an acute lethal pneumonia, supported by high bacterial burdens, severe inflammatory cells infiltration and lung damage. The lung transcriptome changes in response to lethal pneumonia were detected by RNA sequencing. The results showed that 6,288 host genes changed expression, with 3,313 upregulated genes and 2,975 downregulated genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that genes related to TNF, cytokine-cytokine receptor interaction, Toll-like receptor, NOD-like receptor, NF-κB, Jak-STAT, HIF-1 signaling pathways, apoptosis, and phagosome were significantly upregulated. Whereas, genes associated with PI3K-AKT signaling pathway, glycolysis/gluconeogenesis, amino acid and fatty acid metabolism were downregulated. Immune cell typing highlighted the inflammatory response of innate immune cells headed by neutrophils. The reliability of RNA sequencing results were verified with selected differentially expressed genes by real-time PCR. This work provides an insight into the pathogenesis of lethal lung infection.

摘要

是医院获得性肺炎的主要病因之一,然而,关于与感染发病机制相关的宿主免疫反应却知之甚少。在此,我们使用一种高毒力菌株建立了急性致死性肺炎,其特征为高细菌载量、严重的炎性细胞浸润和肺损伤。通过RNA测序检测了致死性肺炎诱导的肺转录组变化。结果显示,6288个宿主基因发生表达变化,其中3313个基因上调,2975个基因下调。基因本体论和京都基因与基因组百科全书通路分析显示,与肿瘤坏死因子、细胞因子-细胞因子受体相互作用、Toll样受体、NOD样受体、核因子κB、Jak-STAT、低氧诱导因子-1信号通路、凋亡和吞噬体相关的基因显著上调。而与磷脂酰肌醇-3激酶-蛋白激酶B信号通路、糖酵解/糖异生、氨基酸和脂肪酸代谢相关的基因下调。免疫细胞分型突出了以中性粒细胞为首的固有免疫细胞的炎症反应。通过实时PCR对选定的差异表达基因验证了RNA测序结果的可靠性。这项工作为致死性肺部感染的发病机制提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d083/7188829/876eeb8b59d1/fimmu-11-00708-g0007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d083/7188829/876eeb8b59d1/fimmu-11-00708-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d083/7188829/346a5b0ac03e/fimmu-11-00708-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d083/7188829/da5e2e839ffa/fimmu-11-00708-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d083/7188829/f15509be0484/fimmu-11-00708-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d083/7188829/14b19dc81c86/fimmu-11-00708-g0004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d083/7188829/876eeb8b59d1/fimmu-11-00708-g0007.jpg

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