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感染小鼠肺部宿主-病原体相互作用的蛋白质组学全景

Proteomics Landscape of Host-Pathogen Interaction in Infected Mouse Lung.

作者信息

Li Xin, Liu Xiaofen, Horvatovich Peter, Hu Yingwei, Zhang Jing

机构信息

Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.

Key Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family Planning Commission, Shanghai, China.

出版信息

Front Genet. 2021 May 7;12:563516. doi: 10.3389/fgene.2021.563516. eCollection 2021.

Abstract

is an important pathogen of nosocomial infection worldwide, which can primarily cause pneumonia, bloodstream infection, and urinary tract infection. The increasing drug resistance rate of and the slow development of new antibacterial drugs brought great challenges for clinical treatment. Host immunity is crucial to the defense of infection, and understanding the mechanisms of immune response can facilitate the development of new therapeutic strategies. To characterize the system-level changes of host proteome in immune response, we used tandem mass tag (TMT) labeling quantitative proteomics to compare the proteome changes of lungs from infected mice with control mice 6 h after infection. A total of 6,218 proteins were identified in which 6,172 could be quantified. With threshold < 0.05 and relative expression fold change > 1.2 or < 0.83, we found 120 differentially expressed proteins. Bioinformatics analysis showed that differentially expressed proteins after infection were associated with receptor recognition, NADPH oxidase (NOX) activation and antimicrobial peptides. These differentially expressed proteins were involved in the pathways including leukocyte transendothelial migration, phagocyte, neutrophil degranulation, and antimicrobial peptides. In conclusion, our study showed proteome changes in mouse lung tissue due to infection and suggested the important roles of NOX, neutrophils, and antimicrobial peptides in host response. Our results provide a potential list of protein candidates for the further study of host-bacteria interaction in infection. Data are available via ProteomeXchange with identifier PXD020640.

摘要

是全球医院感染的重要病原体,主要可引起肺炎、血流感染和尿路感染。其耐药率不断上升以及新型抗菌药物研发缓慢给临床治疗带来了巨大挑战。宿主免疫对于抵御感染至关重要,了解免疫反应机制有助于开发新的治疗策略。为了表征宿主蛋白质组在免疫反应中的系统水平变化,我们使用串联质谱标签(TMT)标记定量蛋白质组学来比较感染后6小时感染小鼠与对照小鼠肺部的蛋白质组变化。共鉴定出6218种蛋白质,其中6172种可被定量。以P < 0.05和相对表达倍数变化> 1.2或< 0.83为阈值,我们发现了120种差异表达蛋白质。生物信息学分析表明,感染后差异表达的蛋白质与受体识别、NADPH氧化酶(NOX)激活和抗菌肽有关。这些差异表达蛋白质参与了包括白细胞跨内皮迁移、吞噬细胞、中性粒细胞脱颗粒和抗菌肽在内的途径。总之,我们的研究显示了感染导致的小鼠肺组织蛋白质组变化,并提示了NOX、中性粒细胞和抗菌肽在宿主反应中的重要作用。我们的结果为进一步研究感染中宿主-细菌相互作用提供了一份潜在的蛋白质候选清单。数据可通过ProteomeXchange获得,标识符为PXD020640。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/735f/8138179/f8efc1688c30/fgene-12-563516-g001.jpg

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