抗TLR2抗体抑制小鼠金黄色葡萄球菌肺炎炎症反应

Anti-TLR2 antibody attenuates inflammatory response of Staphylococcus aureus pneumonia in mice

目的:探讨抗TLR2抗体抑制TLR2信号通路对小鼠金黄色葡萄球菌(SA)肺炎炎症反应的影响。方法:将60只C57BL/6J小鼠,随机分为:正常组、SA肺炎组和抗TLR2抗体组,分别按接种后3、8 d各分2小组。正常组小鼠滴鼻接种无菌PBS,SA肺炎组小鼠接种SA菌悬液,抗TLR2抗体组小鼠先尾静脉注射抗TLR2抗体,再接种SA菌悬液,在预定时间点处死小鼠,取肺泡灌洗液(BALF)计算载菌量、白细胞数及中性粒细胞比值,用酶联免疫吸附法测定BALF及血清KC、IL-10含量,HE染色观察肺部病理变化及免疫组化检测肺组织TLR2表达。结果:滴鼻接种后第3天,与正常组比较,感染SA后小鼠BALF及血清中KC、IL-10表达明显升高,HE病理改变明显。抗TLR2抗体组小鼠较SA肺炎组BALF载菌量高,白细胞计数及中性粒细胞比值降低,BALF和血清KC表达水平降低,而IL-10无明显差异,HE病理评分降低。滴鼻接种后第8天,抗TLR2抗体组小鼠HE病理评分明显低于SA肺炎组,而BALF载菌量无明显差异。结论:抗TLR2抗体可抑制小鼠SA肺炎炎症介质的释放,减少炎症细胞浸润,从而减轻肺部炎症反应。

Objective：To investigate the effects of the anti-TLR2 antibody blocking TLR2 signaling pathway on inflammatory response in Staphylococcus aureus pneumonia murine models.Methods： Sixty C57BL/6J mice were divided randomly into normal control,SA pneumonia,and anti-TLR2 antibody group,killed 3 and 8 days after inoculation respectively.Normal control mice inoculated sterile PBS intranasally ,SA pneumonia mice inoculated SA ,anti-TLR2 antibody group of mice injected with anti-TLR2 antibody by tail vein and then inoculated SA intranasally.At the predetermined point , the colony-forming units （ CFU ） of bacteria were higher , leukocytes and neutrophil percentage were counted in bronchoalveolar lavage fluid （ BALF ） , the concentrations of KC and IL-10 in BALF and serum were assayed by ELISA ,changes in pulmonary histopathology were observed with HE staining and TLR 2 expression was detected by immunohistochemical.Results：3 days after intranasal inoculation ,the concentrations of KC and IL-10 in BALF and serum was increased in SA pneumonia mice , pulmonary histopathology changes significantly in HE staining.Compared with SA pneumonia mice,the CFU of bacteria were higher,leukocytes count and neutrophil percentage ,the concentrations of KC in BALF and serum,as well as HE pathological scores were reduced significantly in anti-TLR2 antibody group mice ,while no significant difference in IL-10.8 days after intranasal inoculation , HE pathological scores of anti-TLR2 antibody group mice were significantly lower than SA pneumonia group mice ,the CFU of bacteria in BALF were not statistically different between those two groups.Conclusion：Anti-TLR2 antibody attenuates the production of inflammatory mediators and inflammatory cell infiltration in SA pneumonia mice .