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弓形虫感染的严重联合免疫缺陷(SCID)小鼠及人外周血淋巴细胞移植的SCID小鼠组织中寄生虫各阶段的分布

Distribution of parasite stages in tissues of Toxoplasma gondii infected SCID mice and human peripheral blood lymphocyte-transplanted SCID mice.

作者信息

Meyer D J, Allan J E, Beaman M H

机构信息

Department of Medicine, University of Western Australia, Australia.

出版信息

Parasite Immunol. 2000 Nov;22(11):567-79. doi: 10.1046/j.1365-3024.2000.00338.x.

Abstract

The establishment of Toxoplasma gondii infection in the tissues of SCID mice and SCID mice transplanted with human peripheral blood lymphocytes (PBL) was investigated. The presence of bradyzoites and tachyzoites was analysed in hu-PBL SCID mice using Southern blot of reverse transcriptase-polymerase chain reaction products for the expression of B1, BAG1 and SAG1 of T. gondii. BAG1 was present by week 1 in brain, lung, liver and spleen of some animals; by week 3, BAG1 was present in all animals and in all of these tissues. In contrast, SAG1 was rarely detected until week 2 (mainly in the lung and brain) and by week 3, some animals still did not have detectable SAG1 in brain, lung, liver and spleen. SAG1 expression was increased in the lungs of animals transplanted with human PBL compared to nontransplanted SCID mice. Human PBL engraftment was demonstrated, initially in uninfected mice, by the presence of human CD3+ T cells in the spleen (3.1 x 10(5) positive cells) and peritoneal cavity (3.4 x 10(5) cells) 4 weeks after transplantation. The final outcome of infection was not influenced by the presence of human PBL, with similar mortality in human PBL transplanted and nontransplanted mice. These studies provide a detailed analysis of the kinetics and distribution of both the cyst and tachyzoite stage of T. gondii. This system has been established to allow evaluation of therapies against T. gondii immunodeficient mice in the presence of human immune cells.

摘要

研究了弓形虫在重症联合免疫缺陷(SCID)小鼠组织以及移植了人外周血淋巴细胞(PBL)的SCID小鼠组织中的感染情况。使用逆转录酶-聚合酶链反应产物的Southern印迹法分析hu-PBL SCID小鼠中缓殖子和速殖子的存在情况,以检测弓形虫B1、BAG1和SAG1的表达。在部分动物的脑、肺、肝和脾中,第1周时可检测到BAG1;到第3周时,所有动物的所有这些组织中均有BAG1存在。相比之下,直到第2周才很少检测到SAG1(主要在肺和脑中),到第3周时,一些动物的脑、肺、肝和脾中仍未检测到可检测水平的SAG1。与未移植的SCID小鼠相比,移植了人PBL的动物肺中SAG1表达增加。在未感染的小鼠中,移植后4周,通过脾中存在人CD3+ T细胞(3.1×10⁵个阳性细胞)和腹腔中存在人CD3+ T细胞(3.4×10⁵个细胞)证明了人PBL的植入。感染的最终结果不受人PBL存在的影响,移植了人PBL的小鼠和未移植的小鼠死亡率相似。这些研究详细分析了弓形虫包囊和速殖子阶段的动力学和分布情况。已建立该系统以评估在存在人免疫细胞的情况下针对弓形虫免疫缺陷小鼠的治疗方法。

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