Immunogenicity of mycobacterial PPE44 (Rv2770c) in Mycobacterium bovis BCG-infected mice
Immunogenicity of mycobacterial PPE44 (Rv2770c) in Mycobacterium bovis BCG-infected mice
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DOI：
10.1099/jmm.0.45960-0
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发表时间：
2005-05-01
影响因子：
3
通讯作者：
Garzelli, C
中科院分区：
文献类型：
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作者：
Bonanni, D;Rindi, L;Garzelli, C
结核分枝杆菌的Pro-Pro-Glu（PPE）蛋白家族包括69个富含甘氨酸的蛋白，具有保守的N-末端结构域。它们在结核病中的作用尚不清楚，但据推测它们可能具有重要的免疫学意义。本文研究了ppe 44（Rv 2770 c）基因产物在皮下或静脉注射卡介苗（BCG）感染的BALB/c小鼠中的免疫原性。皮下感染的小鼠产生高滴度的抗PPE 44 IgG 1抗体，而PPE 44特异性IgG 2a。在所有测试时间均不存在抗体。来自引流淋巴结和脾脏的PPE 44致敏细胞产生低水平的IFN-γ，并且在PPE 44皮内激发后观察到中度的迟发型超敏反应。在静脉感染的小鼠中，抗PPE 44 IgG 1抗体反应明显高于皮下感染;抗PPE 44 IgG 2a。检测到滴度比IgG 1低约0.5-2.0 log（10）的抗体。干扰素（IFN）-γ的生产在PPE 44刺激的脾细胞培养是短暂的。这些结果表明，PPE 44代表了一种新的分枝杆菌抗原表达在皮下和静脉感染的M。BALB/c小鼠中的牛BCG。两种感染模型似乎都将对PPE 44的免疫应答向Th 2表型转移，如IgG 1同种型优于IgG 2a和低IFN-γ和迟发型超敏反应所证明的。
The Pro-Pro-Glu (PPE) protein family of Mycobacterium tuberculosis includes 69 glycine-rich proteins with a conserved N-terminal domain. Their role in tuberculosis is unknown, but it has been speculated that they may have an important immunological significance. In this investigation, the immunogenicity of the ppe44 (Rv2770c) gene product in BALB/c mice infected subcutaneously or intravenously with Mycobacterium bovis bacille Calmette-Guerin (BCG) was evaluated. Mice infected subcutaneously developed high titres of anti-PPE44 IgG1 antibodies, while PPE44-specific IgG2a. antibodies were absent at all times tested. PPE44-primed cells from draining lymph nodes and spleen produced low levels of IFN-gamma, and a moderate degree of delayed-type hypersensitivity was observed following PPE44 intracutaneous challenge. In mice infected intravenously, the anti-PPE44 IgG1 antibody response was markedly higher compared with the subcutaneous infection; anti-PPE44 IgG2a. antibodies at titres approximately 0.5-2.0 log(10) lower than IgG1 were detected. Interferon (IFN)-gamma production in PPE44-stimulated spleen-cell cultures was transient. These results indicate that PPE44 represents a novel mycobacterial antigen expressed during subcutaneous and intravenous infection by M. bovis BCG in BALB/c mice. Both infection models seem to polarize the immune response to PPE44 towards a Th2 phenotype, as testified by the IgG1 isotype being predominant over IgG2a and by the low IFN-gamma and delayed-type hypersensitivity responses.