Immunometabolism within the tuberculosis granuloma: amino acids, hypoxia, and cellular respiration.
Immunometabolism within the tuberculosis granuloma: amino acids, hypoxia, and cellular respiration.
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DOI：
10.1007/s00281-015-0534-0
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发表时间：
2016-03
影响因子：
9
通讯作者：
Murray PJ
中科院分区：
文献类型：
--
作者：
Qualls JE;Murray PJ
结核（TB）肉芽肿是感染和未感染的巨噬细胞、T细胞、嗜中性粒细胞和其他免疫细胞的紧密、有组织的聚集体。在肉芽肿内，发生了几种独特的代谢适应性改变免疫细胞的行为，可能有利于细菌的持久性与免疫病理学的保护相平衡。这些包括诱导巨噬细胞中的色氨酸酶-1以调节一氧化氮（NO）产生并阻断T细胞增殖，抑制缺氧区域中需要氧的NO产生，以及诱导修饰T细胞增殖和功能的色氨酸降解酶。肉芽肿的空间和时间依赖性组织进一步影响免疫代谢，例如通过活化的巨噬细胞产生乳酸，其可以诱导β-内酰胺酶-1。虽然复杂，结核肉芽肿内和周围的代谢变化可以通过宿主导向疗法进行潜在的修改。虽然消除结核杆菌通常是任何抗结核治疗的目标，但针对宿主的方法也必须考虑到对肺的免疫病理损伤的可能性。
Tuberculosis (TB) granulomas are compact, organized agglomerations of infected and uninfected macrophages, T cells, neutrophils and other immune cells. Within the granuloma, several unique metabolic adaptations occur to modify the behavior of immune cells, potentially favoring bacterial persistence balanced with protection against immunopathology. These include the induction of arginase-1 in macrophages to temper nitric oxide (NO) production and block T cell proliferation, inhibition of oxygen-requiring NO production in hypoxic regions, and induction of tryptophan degrading enzymes that modify T cell proliferation and function. The spatial and time dependent organization of granulomas further influences immunometabolism, for example through lactate production by activated macrophages, which can induce arginase-1. Although complex, the metabolic changes in and around TB granulomas can be potentially modified by host-directed therapies. While elimination of the TB bacilli is often the goal of any anti-TB therapy, host-directed approaches must also account for the possibility of immunopathologic damage to the lung.