编码半胱氨酸蛋白酶的多个CPB基因的表达是墨西哥利什曼原虫体内毒力所必需的。
Expression of multiple CPB genes encoding cysteine proteases is required for Leishmania mexicana virulence in vivo.
作者信息
Denise Hubert, McNeil Kathryn, Brooks Darren R, Alexander James, Coombs Graham H, Mottram Jeremy C
机构信息
Wellcome Centre for Molecular Parasitology, The Anderson College, University of Glasgow, United Kingdom.
出版信息
Infect Immun. 2003 Jun;71(6):3190-5. doi: 10.1128/IAI.71.6.3190-3195.2003.
Abstract
Leishmania mexicana mutants deficient in the multicopy CPB gene array have reduced virulence, demonstrated by poor lesion growth in BALB/c mice and induction of a protective Th1 response. Reinsertion of the amastigote-specific CPB2.8 or metacyclic stage-specific CPB2 gene into a CPB-deficient mutant L. mexicana failed to restore either a Th2 response or sustained virulence. However, reexpression of multiple CPB genes from a cosmid significantly restored virulence. This was characterized by increased lesion and parasite growth and the acquisition of a Th2 response, as determined by measuring interleukin-4 production and immunoglobulin G1 (IgG1) and IgE levels. These studies confirm that L. mexicana cysteine proteases are important virulence factors and provide an explanation for the presence in L. mexicana of a multicopy tandem array of CPB genes.
摘要
多拷贝CPB基因阵列缺陷的墨西哥利什曼原虫突变体毒力降低，这在BALB/c小鼠的病变生长不良以及诱导保护性Th1反应中得到证明。将无鞭毛体特异性CPB2.8或前循环期特异性CPB2基因重新插入CPB缺陷的墨西哥利什曼原虫突变体中，未能恢复Th2反应或持续毒力。然而，从黏粒中重新表达多个CPB基因可显著恢复毒力。这表现为病变和寄生虫生长增加，并获得Th2反应，这是通过测量白细胞介素-4的产生以及免疫球蛋白G1（IgG1）和IgE水平来确定的。这些研究证实，墨西哥利什曼原虫半胱氨酸蛋白酶是重要的毒力因子，并为墨西哥利什曼原虫中存在多拷贝串联CPB基因阵列提供了解释。
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