摘要
Cathelicidin抗菌肽系多物种保守的具有天然广谱抗微生物活性的小分子多肽。本研究旨在探究金环蛇抗菌肽cathelicidin-BF是否可以激活宿主抗金黄色葡萄球菌感染免疫。在金黄色葡萄球菌(Staphylococcus aureus, S.aureus)感染前24、8和4h给C57BL/6小鼠腹腔注射抗菌肽cathelicidin-BF(10mg/kg),或等体积PBS为对照,0h经腹腔注射S.aureus或耐甲氧西林金黄色葡萄球菌(methicillin-resistant S.aureus, MRSA),18h后计数小鼠腹水菌落形成单位(colony forming unit, CFU)。实验发现抗菌肽cathelicidin-BF注射组小鼠腹水细菌CFU显著低于对照组,表明预注射cathelicidin-BF能显著增强小鼠抗S.aureus感染。为明确抗菌肽是否通过调节小鼠固有免疫应答而达到抗菌效果,流式分析注射抗菌肽后小鼠腹水中各免疫细胞亚群发现:cathelicidin-BF显著促进了单核/巨噬细胞和中性粒细胞在腹腔的富集。进一步分析发现,抗菌肽在体内可促进小鼠腹腔中单核细胞及中性粒细胞趋化因子CCL2、CXCL1、CXCL2表达;体外则以剂量依赖方式促进小鼠巨噬细胞分泌趋化因子。Cathelicidin-BF还能激活小鼠腹腔巨噬细胞MAPK和NF-κB信号通路。以上结果表明,抗菌肽cathelicidin-BF可通过增强小鼠巨噬细胞/中性粒细胞固有免疫加强小鼠抗S.aureus感染。
Cathelicidins are one family of evolutionarily conserved antimicrobial peptides(AMPs),possessing broad-spectrum of antibacterial,antiviral,and immune modulatory activities.This study was aimed to explore whether cathelicidin-BF fromB.fasciatus could enhance host anti-bacterial innate immunity against S.aureus infection.C57 BL/6 mice were intraperitoneally injected with antibacterial peptide cathelicidin-BF(10 mg/kg)at-24 h,-8 hand-4 hbefore S.aureusinfection,and equal volume of PBS was used in the control mice.After intraperitoneal injection of S.aureus or methicillin-resistant S.aureus(MRSA),mouse ascites colony forming unit(CFU)was counted 18 hlater.Cathelicidin-BF pre-injection significantly reduced the ascites bacterial CFU as compared to PBS,indicating that pre-cathelicidin-BF existence significantly enhances host resistance to S.aureus infection.In order to clarify the immune-modulating mechanism of cathelicidin-BF-mediated antibacterial effect,immune cell composition in the ascites of mice after cathelicidin-BF injection was analysed by flow cytometry.It revealed that cathelicidin-BF pre-injection significantly promoted the recruitment of monocytes/macrophages and neutrophils into the peritoneal cavity of mice.Further analysis showed that cathelicidin-BF enhanced CCL2,CXCL1,CXCL2 chemokines production in the peritoneal cavity and in mouse macrophages in a dose-dependent manner.In addition,cathelicidin-BF activates MAPK and NF-κB signaling pathway in mouse peritoneal macrophages.Taken together,we first demonstrate that the antibacterial peptide cathelicidin-BF can enhance host resistance to S.aureusinfection via up-regulating anti-bacterial macrophage/neutrophil innate immunity.
作者
周延东
罗自为
杨佩佩
卫林
徐薇
ZHOU Yan-dong;LUO Zi-wei;YANG Pei-pei;WEI Lin;XU Wei(Institutes of Biology and Medical Sciences,Soochow University,Suzhou 215123,China)
出处
《现代免疫学》
CAS
CSCD
北大核心
2018年第6期449-455,共7页
Current Immunology
基金
国家自然科学基金(31470869
31870903)
