一种新的针对甲氧西林抗性金黄色葡萄球菌（MRSA）感染的免疫逃避策略：基于补体模拟抗生素递送系统的补体免疫治疗模拟,Advanced Therapeutics

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一种新的针对甲氧西林抗性金黄色葡萄球菌（MRSA）感染的免疫逃避策略：基于补体模拟抗生素递送系统的补体免疫治疗模拟
Advanced Therapeutics ( IF 3.7 ) Pub Date : 2020-12-18 , DOI: 10.1002/adtp.202000167
Xucheng Hou _{1,

2} , Wenxi Zhang ₁ , Yansha Meng ₁ , Wenkai Zhou ₂ , Guanghua Peng ₁ , Jiongxi Lei ₁ , Shuangchen Cong ₁ , Maoyuan Song ₁ , Guiling Li ₂ , Xinru Li ₁

Affiliation

耐甲氧西林金黄色葡萄球菌（MRSA）会干扰宿主的协同防御，从而逃避免疫监视。在此，提出了一种模拟补体疗法的新的免疫疗法策略。Tat细胞穿透肽和小麦胚芽凝集素是两种人工效应物，用于开发多功能补体模拟脂质体（CML），同时递送抗生素并与巨噬细胞协调补体系统。CML成功地模拟了补体系统的功能，包括形成膜攻击复合物，调理吞噬作用和吞噬细胞的激活。在感染部位，CML能够识别MRSA并破坏细菌渗透屏障（细胞壁和细胞膜）。同时，附着于MRSA表面的CML能够激活巨噬细胞的吞噬作用和免疫反应。结果，CML在体外和巨噬细胞中均显着提高了克拉霉素的细菌活性。此外，CML在三种感染模型（包括皮肤脓肿，肺炎和菌血症小鼠模型）中有效减轻了MRSA负担。因此，CML提供了克服细菌免疫逃逸的新策略，并为传染病免疫疗法的发展提供了启示。

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A New Anti‐Immune Evasion Strategy against Methicillin‐Resistant Staphylococcus Aureus (MRSA) Infections: Simulating Complement Immunotherapy Based on Complement‐Mimic Antibiotic Delivery System

Methicillin‐resistant Staphylococcus aureus (MRSA) can interfere with synergistic host defenses, thus escaping from immune surveillance. Herein, a new immunotherapy strategy‐simulating complement therapy is proposed. Two artificial effectors, Tat cell penetrating peptide and wheat germ agglutinin, are utilized to develop a multifunctional complement‐mimic liposome (CML) simultaneously delivering antibiotics and orchestrating the complement system with macrophages. The CML successfully simulates the functions of the complement system, including formation of a membrane attack complex, mediation of opsonophagocytosis, and activation of phagocytes. At infection sites, CMLs are able to recognize MRSA and disrupt bacterial permeation barriers (cell walls and cell membranes). Meanwhile, CMLs attached to the surface of MRSA are able to activate the phagocytosis and immune responses of macrophages. As a result, CMLs significantly increased the bacterial activity of clarithromycin both in vitro and in macrophages. Moreover, CMLs effectively reduced the MRSA burden in three infection models, including skin abscesses, pneumonia, and bacteremia mouse models. Therefore, the CML provides a novel strategy for overcoming bacterial immune evasion and sheds light on the development of immunotherapies for infectious diseases.

更新日期：2020-12-18

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