Leishmania major LACK antigen is required for efficient vertebrate parasitization.
Leishmania major LACK antigen is required for efficient vertebrate parasitization.
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DOI：
10.1084/jem.20031162
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发表时间：
2003-12-01
期刊：
影响因子：
--
通讯作者：
Locksley RM
中科院分区：
文献类型：
--
作者：
Kelly BL;Stetson DB;Locksley RM
主要利什曼原虫LACK抗原是易感BALB/c小鼠免疫应答的关键靶标，并且仍然是人类利什曼病的可行疫苗候选物。我们描述了四个缺乏基因的基因组组织在L。主要二倍体基因组以及选择的结果缺乏基因打靶。在上游或下游位点中含有单一缺失基因的寄生虫在体外与野生型前鞭毛体相似地生长，但即使在T细胞缺陷的环境中也未能有效地寄生BALB/c小鼠。在体外巨噬细胞中，单拷贝缺失突变体作为无鞭毛体的复制被减弱，并且寄生虫在免疫缺陷小鼠中的数量未能增加，尽管它们持续数月。与额外的缺失拷贝互补足以诱导稳健的病变发展，这也发生在使用具有两个缺失基因的寄生虫时。相反，尝试产生缺乏无效的寄生虫失败，这表明LACK是寄生虫生存所必需的。这些数据表明，LACK是有效的哺乳动物寄生的关键，因此代表了一个潜在的药物靶点利什曼病。
The Leishmania major LACK antigen is a key target of the immune response in susceptible BALB/c mice and remains a viable vaccine candidate for human leishmaniasis. We describe the genomic organization of the four lack genes in the L. major diploid genome together with results of selected lack gene targeting. Parasites containing a single lack gene in either the upstream or downstream locus grew comparably to wild-type promastigotes in vitro, but failed to parasitize BALB/c mice efficiently, even in a T cell–deficient environment. The replication of single copy lack mutants as amastigotes was attenuated in macrophages in vitro, and parasites failed to increase in numbers in immunodeficient mice, despite their persistence over months. Complementation with an additional lack copy was sufficient to induce robust lesion development, which also occurred using parasites with two lack genes. Conversely, attempts to generate lack-null parasites failed, suggesting that LACK is required for parasite viability. These data suggest that LACK is critical for effective mammalian parasitization and thus represents a potential drug target for leishmaniasis.
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影响因子：
5.3
作者：
Chang, BY;Conroy, KB;Cartwright, CA
通讯作者：
Cartwright, CA
DOI：
10.1084/jem.191.12.2121
发表时间：
2000-06-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bogdan C;Donhauser N;Döring R;Röllinghoff M;Diefenbach A;Rittig MG
通讯作者：
Rittig MG
影响因子：
3.1
作者：
Bourreau, E;Prévot, G;Launois, P
通讯作者：
Launois, P
影响因子：
4.8
作者：
Liliental, J;Chang, DD
通讯作者：
Chang, DD
影响因子：
56.9
作者：
Julia, V;Rassoulzadegan, M;Glaichenhaus, N
通讯作者：
Glaichenhaus, N