MASP1调节作为重症小儿百日咳的新治疗靶点:来自多组学方法的见解。

IF 2.9 3区 医学 Q3 IMMUNOLOGY Infection and Immunity Pub Date : 2025-02-18 Epub Date: 2025-01-22 DOI:10.1128/iai.00271-24
Lin Xu, Caiying Wang, Yuhuan Liu, Yanlan Zhang, Zhen Li, Lin Pang
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引用次数: 0

摘要

百日咳是一种严重的儿童传染病,近年来日益突出。本研究旨在通过多组学分析探讨MASP1蛋白在儿童重症百日咳中的作用,为开发新的治疗策略提供理论依据。本研究从公共数据库中检索儿童百日咳宏基因组和16S rRNA数据,分析微生物多样性和特定菌群丰度,进行途径功能富集分析。通过转录组数据的差异表达分析和基因本体(GO)/京都基因与基因组百科全书(KEGG)功能富集分析,结合机器学习,鉴定出关键基因MASP1。利用人支气管上皮细胞系HBE135-E6E7建立百日咳杆菌感染模型,通过构建过表达和低表达MASP1的细胞系,验证MASP1的表达变化,探讨其与气道上皮细胞损伤的关系。最后,利用小鼠百日咳感染模型评估抑制MASP1表达对感染症状的影响。结果显示,健康儿童和百日咳儿童的微生物多样性和特定菌群丰度存在显著差异,MASP1在严重百日咳中显著上调,其抑制作用减轻了感染症状。该研究强调了MASP1在百日咳中的关键作用,为开发针对MASP1的治疗策略提供了重要的基础。
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MASP1 modulation as a novel therapeutic target in severe pediatric pertussis: insights from a multi-omics approach.

Pertussis, a severe infectious disease in children, has become increasingly prominent in recent years. This study aims to investigate the role of the MASP1 protein in severe pertussis in children through multi-omics analysis, providing a theoretical basis for the development of novel therapeutic strategies. The study retrieved macro-genome and 16S rRNA data of pediatric pertussis from public databases to analyze microbial diversity and specific flora abundance, conducting pathway functional enrichment analysis. Differential expression analysis of transcriptome data and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis, combined with machine learning, identified the key gene MASP1. A Bordetella pertussis infection model was established using human bronchial epithelial cell line HBE135-E6E7 to validate MASP1 expression changes and investigate its relationship with airway epithelial cell damage by constructing cell lines overexpressing and knocking down MASP1. Finally, the impact of inhibiting MASP1 expression on infection symptoms was evaluated using a mouse pertussis infection model. The results revealed significant differences in microbial diversity and specific flora abundance between healthy children and those with pertussis, with MASP1 significantly upregulated in severe pertussis and its inhibition alleviating infection symptoms. The study highlights the critical role of MASP1 in pertussis, providing a crucial foundation for developing therapeutic strategies targeting MASP1.

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来源期刊
Infection and Immunity
Infection and Immunity 医学-传染病学
CiteScore
6.00
自引率
6.50%
发文量
268
审稿时长
3 months
期刊介绍: Infection and Immunity (IAI) provides new insights into the interactions between bacterial, fungal and parasitic pathogens and their hosts. Specific areas of interest include mechanisms of molecular pathogenesis, virulence factors, cellular microbiology, experimental models of infection, host resistance or susceptibility, and the generation of innate and adaptive immune responses. IAI also welcomes studies of the microbiome relating to host-pathogen interactions.
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