Modulation of the arginase pathway in the context of microbial pathogenesis: a metabolic enzyme moonlighting as an immune modulator.
Modulation of the arginase pathway in the context of microbial pathogenesis: a metabolic enzyme moonlighting as an immune modulator.
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DOI：
10.1371/journal.ppat.1000899
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发表时间：
2010-06-17
期刊：
影响因子：
6.7
通讯作者：
Chakravortty D
中科院分区：
文献类型：
--
作者：
Das P;Lahiri A;Lahiri A;Chakravortty D
精氨酸是一种重要的氨基酸，在感染期间用于调节细胞免疫反应。精氨酸也是诱导型一氧化氮合酶（iNOS）和精氨酸酶的共同底物。精氨酸产生的一氧化氮负责有效的免疫应答和宿主细胞的细胞毒性，以杀死入侵的病原体。另一方面，精氨酸通过精氨酸酶途径转化为鸟氨酸和尿素可以支持细菌和寄生病原体的生长。因此，iNOS和精氨酸酶之间的竞争可以导致几种寄生虫和细菌感染的结果。脊椎动物的精氨酸酶有两种亚型，它们都催化精氨酸转化为鸟氨酸和尿素，但它们在组织分布和亚细胞定位方面不同。在感染分枝杆菌属、利什曼原虫属、锥虫属、螺杆菌属、血吸虫属和沙门氏菌属的情况下，已经显示出，脱氢酶同种型通过各种方式调节感染的病理学。尽管存在大量关于哺乳动物精氨酸代谢及其在免疫学中的作用的证据，但病原生物转移宿主精氨酸库作为生存策略的关键选择在感染生物学中仍然是一个谜。
Arginine is a crucial amino acid that serves to modulate the cellular immune response during infection. Arginine is also a common substrate for both inducible nitric oxide synthase (iNOS) and arginase. The generation of nitric oxide from arginine is responsible for efficient immune response and cytotoxicity of host cells to kill the invading pathogens. On the other hand, the conversion of arginine to ornithine and urea via the arginase pathway can support the growth of bacterial and parasitic pathogens. The competition between iNOS and arginase for arginine can thus contribute to the outcome of several parasitic and bacterial infections. There are two isoforms of vertebrate arginase, both of which catalyze the conversion of arginine to ornithine and urea, but they differ with regard to tissue distribution and subcellular localization. In the case of infection with Mycobacterium, Leishmania, Trypanosoma, Helicobacter, Schistosoma, and Salmonella spp., arginase isoforms have been shown to modulate the pathology of infection by various means. Despite the existence of a considerable body of evidence about mammalian arginine metabolism and its role in immunology, the critical choice to divert the host arginine pool by pathogenic organisms as a survival strategy is still a mystery in infection biology.
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