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鉴定卡他莫拉菌表面抗原作为慢性阻塞性肺疾病中人血清抗体反应的靶点

Identification of surface antigens of Moraxella catarrhalis as targets of human serum antibody responses in chronic obstructive pulmonary disease.

作者信息

Murphy Timothy F, Brauer Aimee L, Aebi Christoph, Sethi Sanjay

机构信息

VA Western New York Healthcare System, Medical Research 151, 3495 Bailey Avenue, Buffalo, NY 14215, USA.

出版信息

Infect Immun. 2005 Jun;73(6):3471-8. doi: 10.1128/IAI.73.6.3471-3478.2005.

Abstract

Moraxella catarrhalis is an important respiratory tract pathogen, causing otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). Adults with COPD make antibody responses to M. catarrhalis following infection, but little is known about the identity of the antigens to which these antibodies are directed. In this study, 12 serum samples obtained from adults with COPD who had cleared M. catarrhalis from the respiratory tract following infection and who had developed new serum immunoglobulin G (IgG) to their infecting strain were subjected to a series of assays to identify the antigens to which potentially protective antibodies were directed. Sera were adsorbed with intact bacterial cells, and antibodies were eluted from the surfaces of the bacteria. Analysis by flow cytometry established that adsorption and elution effectively detected antibodies specifically directed to surface-exposed epitopes. Immunoblot assays of adsorbed and eluted serum fractions were performed with purified outer membranes and purified lipooligosaccharide of homologous infecting strains and with a series of mutants deficient in expression of individual outer membrane proteins (OMPs). While heterogeneity in antibody responses among individuals was observed, five major OMPs, UspA1, UspA2, Hag, TbpB, and OMP CD, were identified as targets of antibodies to surface epitopes in the majority of adults with COPD who cleared the organism. These results have important implications in understanding human immune responses to M. catarrhalis and in elucidating the elements of a protective immune response.

摘要

卡他莫拉菌是一种重要的呼吸道病原体,可导致儿童中耳炎以及慢性阻塞性肺疾病(COPD)成人患者的下呼吸道感染。COPD成人患者在感染卡他莫拉菌后会产生抗体反应,但对于这些抗体所针对的抗原的具体情况却知之甚少。在本研究中,从呼吸道已清除卡他莫拉菌且针对感染菌株产生了新的血清免疫球蛋白G(IgG)的COPD成人患者中获取了12份血清样本,对其进行了一系列检测,以确定潜在保护性抗体所针对的抗原。血清用完整细菌细胞吸附,抗体从细菌表面洗脱。通过流式细胞术分析确定,吸附和洗脱有效地检测到了特异性针对表面暴露表位的抗体。用同源感染菌株的纯化外膜和纯化脂寡糖以及一系列单个外膜蛋白(OMP)表达缺陷的突变体对吸附和洗脱后的血清组分进行免疫印迹分析。虽然观察到个体间抗体反应存在异质性,但在大多数清除该病原体的COPD成人患者中,五种主要的OMP,即UspA1、UspA2、Hag、TbpB和OMP CD,被确定为针对表面表位抗体的靶点。这些结果对于理解人类对卡他莫拉菌的免疫反应以及阐明保护性免疫反应的要素具有重要意义。

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