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梅毒螺旋体亚种和菌株以及其他致病性密螺旋体中15千道尔顿脂蛋白的保守性:遗传和抗原分析

Conservation of the 15-kilodalton lipoprotein among Treponema pallidum subspecies and strains and other pathogenic treponemes: genetic and antigenic analyses.

作者信息

Centurion-Lara A, Arroll T, Castillo R, Shaffer J M, Castro C, Van Voorhis W C, Lukehart S A

机构信息

Department of Medicine, University of Washington, Seattle 98195, USA.

出版信息

Infect Immun. 1997 Apr;65(4):1440-4. doi: 10.1128/iai.65.4.1440-1444.1997.

Abstract

The 15-kDa lipoprotein of Treponema pallidum is a major immunogen during natural syphilis infection in humans and experimental infection in other hosts. The humoral and cellular immune responses to this molecule appear late in infection as resistance to reinfection is developing. One therefore might hypothesize that this antigen is important for protective immunity. This possibility is explored by using both genetic and antigenic approaches. Limited or no cross-protection has been demonstrated between the T. pallidum subspecies and strains or between Treponema species. We therefore hypothesized that if the 15-kDa antigen was of major importance in protective immunity, it might be a likely site of antigenic diversity. To explore this possibility, the sequences of the open reading frames of the 15-kDa gene have been determined for Treponema pallidum subsp. pallidum (Nichols and Bal-3 strains), T. pallidum subsp. pertenue (Gauthier strain), T. pallidum subsp. endemicum (Bosnia strain), Treponema paraluiscuniculi (Cuniculi A, H, and K strains), and a little-characterized simian isolate of Treponema sp. (Fribourg-Blanc strain). No significant differences in DNA sequences of the genes for the coding region of the 15-kDa antigen were found among the different species and subspecies studied. In addition, all organisms showed expression of the 15-kDa antigen as determined by monoclonal antibody staining. The role of the 15-kDa antigen in protection against homologous infection with T. pallidum subsp. pallidum Nichols was examined in rabbits immunized with a purified recombinant 15-kDa fusion protein. No alteration in chancre development was observed in immunized, compared to unimmunized, rabbits, and the antisera induced by the immunization failed to enhance phagocytosis of T. pallidum subsp. pallidum by macrophages in vitro. These results do not support a major role for this antigen in protection against syphilis infection.

摘要

梅毒螺旋体的15 kDa脂蛋白是人类自然梅毒感染和其他宿主实验性感染期间的主要免疫原。对该分子的体液免疫和细胞免疫反应在感染后期出现,此时对再感染的抵抗力正在形成。因此,有人可能会假设这种抗原对保护性免疫很重要。通过使用遗传和抗原方法来探索这种可能性。在梅毒螺旋体亚种和菌株之间或在密螺旋体属物种之间,已证明存在有限或无交叉保护作用。因此,我们假设,如果15 kDa抗原在保护性免疫中起主要作用,它可能是抗原多样性的一个可能位点。为了探索这种可能性,已确定了梅毒螺旋体亚种苍白亚种(Nichols和Bal - 3菌株)、梅毒螺旋体亚种 pertenue(Gauthier菌株)、梅毒螺旋体亚种endemicum(波斯尼亚菌株)、兔梅毒螺旋体(Cuniculi A、H和K菌株)以及一种特征不明的梅毒螺旋体属猿猴分离株(Fribourg - Blanc菌株)的15 kDa基因开放阅读框的序列。在所研究的不同物种和亚种中,未发现15 kDa抗原编码区基因的DNA序列有显著差异。此外,通过单克隆抗体染色确定,所有生物体均显示出15 kDa抗原的表达。在用纯化的重组15 kDa融合蛋白免疫的兔子中,检测了15 kDa抗原在抵抗梅毒螺旋体亚种苍白亚种Nichols同源感染中的作用。与未免疫的兔子相比,在免疫的兔子中未观察到溃疡发展有改变,并且免疫诱导的抗血清未能增强巨噬细胞在体外对梅毒螺旋体亚种苍白亚种的吞噬作用。这些结果不支持该抗原在预防梅毒感染中起主要作用。

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