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Suppression of Serum Antibody Responses by Pertussis Toxin after Respiratory Tract Colonization by Bordetella pertussis and Identification of an Immunodominant Lipoprotein

机译:百日咳博德特氏菌对呼吸道定殖后百日咳毒素抑制血清抗体应答及免疫脂质蛋白的鉴定

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Pertussis toxin (PT), a virulence factor secreted by Bordetella pertussis, contributes to respiratory tract infection and disease caused by this pathogen. By comparing a wild-type (WT) B. pertussis strain to a mutant strain with an in-frame deletion of the ptx genes encoding PT (ΔPT), we recently found that the lack of PT confers a significant defect in respiratory tract colonization in mice after intranasal inoculation. In this study, we analyzed serum antibody responses in mice infected with the WT or ΔPT strain and found that infection with the ΔPT strain elicited greater responses to several B. pertussis antigens than did infection with the WT, despite the lower colonization level achieved by the ΔPT strain. The same enhanced antibody response was observed after infection with a strain expressing an enzymatically inactive PT; but this response was not observed after infection with B. pertussis mutant strains lacking filamentous hemagglutinin or adenylate cyclase toxin, nor when purified PT was administered with the ΔPT inoculum, indicating a specific role for PT activity in this immunosuppressive effect. In particular, there were consistent strong serum antibody responses to one or more low-molecular-weight antigens after infection with the ΔPT strain. These antigens were Bvg independent, membrane localized, and also expressed by the closely related pathogens Bordetella parapertussis and Bordetella bronchiseptica. Two-dimensional gel electrophoresis and mass spectrometry were used to identify one of the immunodominant low-molecular-weight antigens as a protein with significant sequence homology to peptidoglycan-associated lipoprotein in several other gram-negative bacterial species. However, a serum antibody response to this protein alone did not protect mice against respiratory tract infection by B. pertussis.
机译:百日咳博德特氏菌分泌的毒力因子百日咳毒素(PT)有助于呼吸道感染和由该病原体引起的疾病。通过比较野生型(WT)B。百日咳菌株成为编码PT(ΔPT)的 ptx 基因框内缺失的突变菌株,我们最近发现PT的缺乏在呼吸道定植中具有重大缺陷。鼻内接种后的小鼠。在这项研究中,我们分析了被WT或ΔPT株感染的小鼠的血清抗体反应,发现ΔPT株感染引起对几种 B的更大反应。尽管ΔPT菌株的定植水平较低,但百日咳杆菌抗原还是比WT感染的百分数高。感染表达无酶活性PT的菌株后,观察到相同的增强的抗体反应。但感染 B后未观察到此反应。缺少丝状血凝素或腺苷酸环化酶毒素的百日咳突变菌株,也没有在将纯PT与ΔPT接种物一起施用时显示出PT活性在这种免疫抑制作用中的特定作用。特别地,在用ΔPT菌株感染后,对一种或多种低分子量抗原具有一致的强血清抗体反应。这些抗原是独立于Bvg的,膜定位的,还由密切相关的病原菌副百日咳博德特氏菌支气管博德特氏菌表达。二维凝胶电泳和质谱用于鉴定一种免疫优势的低分子量抗原,该蛋白是与其他几种革兰氏阴性细菌种类中与肽聚糖相关的脂蛋白具有显着序列同源性的蛋白质。但是,仅对这种蛋白质的血清抗体反应不能保护小鼠免受 B的呼吸道感染。百日咳

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