Das S, Barthold S W, Giles S S, Montgomery R R, Telford S R, Fikrig E
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8031, USA.
J Clin Invest. 1997 Mar 1;99(5):987-95. doi: 10.1172/JCI119264.
The temporal synthesis of the P21 protein of Borrelia burgdorferi and the development of the humoral response to this antigen was assessed in infected mice. p21 is a member of the ospE-F gene family and its protein, P21, has been shown to be expressed by B. burgdorferi within infected mice but not by spirochetes cultured in vitro. P21 was not detected on B. burgdorferi in unfed or engorged Ixodes dammini (also known as I. scapularis) ticks, further supporting the postulate that P21 synthesis is specific for the mammalian host. In B. burgdorferi-infected mice, ospE mRNA and OspE antibodies were observed at 7 d, whereas p21 mRNA and P21-specific antibodies were detected at 21-28 d, suggesting that p21 is expressed later than ospE. Moreover, ospA mRNA was not discernible until day 14, indicating that ospA, like p21, is not expressed in the early stages of tick-transmitted murine Lyme borreliosis. Because p21 is expressed during infection in mice, we assessed the human humoral response to P21. 28% (34 of 122) of the patients with either early- or late-stage Lyme disease, and 33% (11 of 33) of the individuals with Lyme arthritis had P21 antibodies, suggesting that a P21 response may serve, at least partially, as a marker of infection. Active immunization with recombinant P21 did not protect C3H mice from tick-borne B. burgdorferi infection, and passive transfer of P21 antiserum to infected mice did not alter the course of disease. These data suggest that the antigenic structure of B. burgdorferi changes during the early stages of murine infection.
在感染小鼠中评估了伯氏疏螺旋体P21蛋白的时间合成以及对该抗原的体液免疫反应的发展。p21是ospE - F基因家族的成员,其蛋白P21已被证明在感染小鼠体内的伯氏疏螺旋体中表达,但在体外培养的螺旋体中不表达。在未进食或饱血的达敏硬蜱(也称为肩突硬蜱)中未检测到伯氏疏螺旋体上的P21,这进一步支持了P21合成对哺乳动物宿主具有特异性的假设。在感染伯氏疏螺旋体的小鼠中,7天时观察到ospE mRNA和OspE抗体,而在21 - 28天时检测到p21 mRNA和P21特异性抗体,这表明p21的表达晚于ospE。此外,直到第14天才可辨别ospA mRNA,表明ospA与p21一样,在蜱传播的小鼠莱姆病早期不表达。由于p21在小鼠感染期间表达,我们评估了人类对P21的体液免疫反应。28%(122例中的34例)的早期或晚期莱姆病患者以及33%(33例中的11例)的莱姆关节炎患者具有P21抗体,这表明对P21的反应可能至少部分地作为感染的标志物。用重组P21进行主动免疫不能保护C3H小鼠免受蜱传播的伯氏疏螺旋体感染,将P21抗血清被动转移到感染小鼠中也不会改变疾病进程。这些数据表明,伯氏疏螺旋体的抗原结构在小鼠感染早期会发生变化。