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恒河猴莱姆病的早期和早期播散阶段:人类感染的模型

Early and early disseminated phases of Lyme disease in the rhesus monkey: a model for infection in humans.

作者信息

Philipp M T, Aydintug M K, Bohm R P, Cogswell F B, Dennis V A, Lanners H N, Lowrie R C, Roberts E D, Conway M D, Karaçorlu M, Peyman G A, Gubler D J, Johnson B J, Piesman J, Gu Y

机构信息

Department of Parasitology, Tulane Regional Primate Research Center, Tulane University Medical Center, Covington, Louisiana 70433.

出版信息

Infect Immun. 1993 Jul;61(7):3047-59. doi: 10.1128/iai.61.7.3047-3059.1993.

Abstract

We demonstrate that Borrelia burgdorferi infection in the rhesus monkey mimics the early and early disseminated phases of human Lyme disease. Clinical, bacteriological, immunological, and pathological signs of infection were investigated during 13 weeks after inoculation of the spirochete. Three animals were given B. burgdorferi (strain JD1) by needle inoculations, six animals were exposed to the bite of B. burgdorferi-infected Ixodes dammini ticks, and three animals were uninfected controls. B. burgdorferi could be recovered from all animals that were given the spirochete. Bacteria were detectable until week 6 postinoculation (p.i.) in blood, until week 8 p.i. in skin biopsies, and at 10 weeks p.i. in the conjunctiva of one of two animals which developed conjunctivitis. Erythema migrans (EM) appeared in one of the three animals infected by needle inoculation and in five of the six animals infected by ticks. Deep dermal perivascular lymphocytic infiltrations (characteristic of human EM) were observed in all animals showing EM clinically. Both EM and conjunctivitis were documented concomitantly with the presence of the spirochete. Lethargy, splenomegaly, and cerebrospinal fluid pleocytosis were also noted in some animals, but the direct connection of these signs with the infection was not shown. The appearance rate of immunoglobulin M and immunoglobulin G antibodies to B. burgdorferi, as well as the antigen spectra recognized, were remarkably similar to those seen in humans. Serum antibodies from infected animals were able to kill B. burgdorferi in vitro in the presence of rhesus complement. The rhesus monkey model appears to be useful for the investigation of the immunology and pathogenesis of Lyme disease and for the development of immunoprophylactic, diagnostic, and chemotherapeutic protocols.

摘要

我们证明,恒河猴感染伯氏疏螺旋体可模拟人类莱姆病的早期和早期播散阶段。在接种螺旋体后的13周内,对感染的临床、细菌学、免疫学和病理学特征进行了研究。三只动物通过针刺接种给予伯氏疏螺旋体(菌株JD1),六只动物暴露于感染伯氏疏螺旋体的达氏硬蜱叮咬,三只动物为未感染对照。在所有接种螺旋体的动物中都能检测到伯氏疏螺旋体。接种后第6周(p.i.)前血液中可检测到细菌,第8周p.i.前皮肤活检中可检测到细菌,在出现结膜炎的两只动物中的一只的结膜中,接种后10周可检测到细菌。游走性红斑(EM)出现在三只经针刺接种感染的动物中的一只以及六只经蜱感染的动物中的五只。在所有临床上出现EM的动物中均观察到深层真皮血管周围淋巴细胞浸润(人类EM的特征)。EM和结膜炎均与螺旋体的存在同时记录。在一些动物中还注意到嗜睡、脾肿大和脑脊液淋巴细胞增多,但未显示这些体征与感染的直接关联。针对伯氏疏螺旋体的免疫球蛋白M和免疫球蛋白G抗体的出现率以及所识别的抗原谱与人类所见非常相似。感染动物的血清抗体在存在恒河猴补体的情况下能够在体外杀死伯氏疏螺旋体。恒河猴模型似乎可用于研究莱姆病的免疫学和发病机制以及开发免疫预防、诊断和化疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9ab/280958/3f0c368c8b31/iai00019-0324-a.jpg

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