Arginine Transport Is Impaired in C57Bl/6 Mouse Macrophages as a Result of a Deletion in the Promoter of Slc7a2 (CAT2), and Susceptibility to Leishmania Infection Is Reduced
Arginine Transport Is Impaired in C57Bl/6 Mouse Macrophages as a Result of a Deletion in the Promoter of Slc7a2 (CAT2), and Susceptibility to Leishmania Infection Is Reduced
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DOI：
10.1093/infdis/jit084
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发表时间：
2013-06-01
影响因子：
6.4
通讯作者：
Celada, Antonio
中科院分区：
文献类型：
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作者：
Gloria Sans-Fons, M.;Yeramian, Andree;Celada, Antonio
宿主遗传因素在免疫反应中发挥着至关重要的作用。为了确定C57 B1/6和BALB-C小鼠之间的差异是否仅仅是由于辅助性T细胞1或辅助性T细胞2产生细胞因子，我们从两种品系获得骨髓来源的巨噬细胞，并将它们与这些细胞因子一起孵育。虽然Nos 2和Arg 1的诱导在2个菌株中是相似的，但对硕大利什曼原虫的感染性不同，巨噬细胞对精氨酸的摄取也不同，这在BALB-C巨噬细胞中更高。阳离子氨基酸转运蛋白SLC 7A 2（也称为“阳离子氨基酸转运蛋白2”或“CAT 2”）的干扰素γ-和白细胞介素4-依赖性诱导的水平在来自C57 B1/6小鼠的巨噬细胞中降低。这种减少是4个AGGG重复序列之一的启动子缺失的结果。这些结果表明，精氨酸的可用性控制巨噬细胞活化的关键方面，并揭示了对利什曼原虫感染的易感性的一个因素。
Host genetic factors play a crucial role in immune response. To determine whether the differences between C57Bl/6 and BALB-C mice are due only to the production of cytokines by T-helper 1 cells or T-helper 2 cells, we obtained bone marrow-derived macrophages from both strains and incubated them with these cytokines. Although the induction of Nos2 and Arg1 was similar in the 2 strains, infectivity to Leishmania major differed, as did macrophage uptake of arginine, which was higher in BALB-C macrophages. The levels of interferon gamma- and interleukin 4-dependent induction of the cationic amino acid transporter SLC7A2 (also known as "cationic amino acid transporter 2," or "CAT2") were decreased in macrophages from C57Bl/6 mice. This reduction was a result of a deletion in the promoter of one of the 4 AGGG repeats. These results demonstrate that the availability of arginine controls critical aspects of macrophage activation and reveal a factor for susceptibility to Leishmania infection.