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Antibodies Against Pseudomonas aeruginosa Alkaline Protease Directly Enhance Disruption of Neutrophil Extracellular Traps Mediated by This Enzyme

文献类型：期刊论文

作者Jing, Chendi1,2; Liu, Chenghua1; Liu, Yu1; Feng, Ruli3; Cao, Run4; Guan, Zhangchun1; Xuan, Bo1; Gao, Yaping1; Wang, Qi5; Yang, Nana6
刊名FRONTIERS IN IMMUNOLOGY
出版日期2021-03-31
卷号12页码:16
ISSN号1664-3224
关键词Pseudomonas aeruginosa alkaline protease alkaline protease inhibitor neutrophil extracellular traps antibody-dependent enhancement
DOI10.3389/fimmu.2021.654649
通讯作者Wang, Hui(wanghui@pkuph.edu.cn) ; Yu, Yanyan(yyy@bjmu.edu.cn) ; Yang, Guang(yangg62033@outlook.com)
英文摘要Extracellular traps released by neutrophils (NETs) are essential for the clearance of Pseudomonas aeruginosa. Alkaline protease (AprA) secreted by P. aeruginosa negatively correlates with clinical improvement. Moreover, anti-AprA in patients with cystic fibrosis (CF) can help identify patients with aggressive forms of chronic infection. However, the mechanism underlying the clinical outcomes remains unclear. We demonstrated that aprA deficiency in P. aeruginosa decreased the bacterial burden and reduced lung infection. AprA degraded NET components in vitro and in vivo but did not affect NET formation. Importantly, antibodies induced by AprA acted as an agonist and directly enhanced the degrading activities of AprA. Moreover, antisera from patients with P. aeruginosa infection exhibited antibody-dependent enhancement (ADE) similar to that of the antibodies we prepared. Our further investigations showed that the interaction between AprA and the specific antibodies might make the enzyme active sites better exposed, and subsequently enhance the recognition of substrates and accelerate the degradation. Our findings revealed that AprA secreted by P. aeruginosa may aggravate infection by destroying formed NETs, an effect that was further enhanced by its antibodies.
资助项目National Natural Science Foundation of China[81871618] ; National Natural Science Foundation of China[31870127] ; Shandong Provincial Major Scientific and Technological Innovation Project (MSTIP)[2019JZZY011012]
WOS研究方向Immunology
语种英语
出版者FRONTIERS MEDIA SA
WOS记录号WOS:000639830400001
源URL[http://119.78.100.183/handle/2S10ELR8/295264]  
专题中国科学院上海药物研究所
通讯作者Wang, Hui; Yu, Yanyan; Yang, Guang
作者单位1.Beijing Inst Pharmacol & Toxicol, State Key Lab Toxicol & Med Countermeasures, Beijing, Peoples R China
2.Peking Univ First Hosp, Dept Infect Dis, Beijing, Peoples R China
3.Peking Univ First Hosp, Dept Clin Lab, Beijing, Peoples R China
4.Henan Univ, Sch Basic Med Sci, Joint Natl Lab Antibody Drug Engn, Kaifeng, Peoples R China
5.Peking Univ, Dept Clin Lab, Peoples Hosp, Beijing, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Mol Pharmacol, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Jing, Chendi,Liu, Chenghua,Liu, Yu,et al. Antibodies Against Pseudomonas aeruginosa Alkaline Protease Directly Enhance Disruption of Neutrophil Extracellular Traps Mediated by This Enzyme[J]. FRONTIERS IN IMMUNOLOGY,2021,12:16.
APA Jing, Chendi.,Liu, Chenghua.,Liu, Yu.,Feng, Ruli.,Cao, Run.,...&Yang, Guang.(2021).Antibodies Against Pseudomonas aeruginosa Alkaline Protease Directly Enhance Disruption of Neutrophil Extracellular Traps Mediated by This Enzyme.FRONTIERS IN IMMUNOLOGY,12,16.
MLA Jing, Chendi,et al."Antibodies Against Pseudomonas aeruginosa Alkaline Protease Directly Enhance Disruption of Neutrophil Extracellular Traps Mediated by This Enzyme".FRONTIERS IN IMMUNOLOGY 12(2021):16.

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来源：上海药物研究所

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