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补体经典激活途径的抑制会损害粪肠球菌感染期间的细菌清除。

Inhibition of the Classical Pathway of Complement Activation Impairs Bacterial Clearance during Enterococcus faecalis Infection.

机构信息

Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.

Department of Microbiology and Immunology, Faculty of Pharmacy, Horus University, New Damietta, Egypt.

出版信息

Infect Immun. 2021 Apr 16;89(5). doi: 10.1128/IAI.00660-20.

Abstract

infections are considered a major public health concern worldwide. The complement system has a crucial role in the protection against different microbial pathogens, including Complement can be activated through three different pathways, including the classical, lectin, and alternative pathways. There is limited information on the role of the classical pathway (CP) in protection against infections caused by In the present study, we generated Fab fragments that successfully block the CP in mouse via inhibition of a key enzyme, C1s-A. Our results showed that anti-C1s-A Fab fragments block CP-mediated C3b and C4b deposition We further showed that administration of anti-C1s-A Fab fragments significantly impairs the CP functional activity Moreover, treatment of mice infected with using anti-C1s-A Fab fragments significantly impairs bacterial clearance as determined from the viable bacterial counts recovered from blood, kidneys, spleens, livers, and lungs of infected mice. Overall, this study highlights the essential role of the CP in host defense against .

摘要

感染被认为是全球主要的公共卫生关注点。补体系统在抵御包括在内的不同微生物病原体方面起着至关重要的作用。补体可以通过三种不同的途径激活,包括经典途径、凝集素途径和替代途径。关于经典途径(CP)在抵御感染中的作用的信息有限。在本研究中,我们通过抑制关键酶 C1s-A 产生了成功阻断小鼠 CP 的 Fab 片段。我们的结果表明,抗 C1s-A Fab 片段阻断 CP 介导的 C3b 和 C4b 沉积。我们进一步表明,给予抗 C1s-A Fab 片段显著损害 CP 的功能活性。此外,用抗 C1s-A Fab 片段处理感染的小鼠,从感染小鼠的血液、肾脏、脾脏、肝脏和肺部中回收的活菌计数可明显损害细菌清除。总的来说,这项研究强调了 CP 在宿主防御中的重要作用。

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