Molecular and cellular mechanisms of Mycobacterium avium-induced thymic atrophy.
Molecular and cellular mechanisms of Mycobacterium avium-induced thymic atrophy.
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DOI：
10.4049/jimmunol.1201525
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发表时间：
2012-10-01
期刊：
影响因子：
--
通讯作者：
Appelberg R
中科院分区：
文献类型：
--
作者：
Borges M;Barreira-Silva P;Flórido M;Jordan MB;Correia-Neves M;Appelberg R
胸腺萎缩被描述为几种病原体感染的结果，并显示通过不同的机制诱导。使用鸟分枝杆菌感染的小鼠模型，我们在这里表明，IFNγ激活的巨噬细胞产生的一氧化氮在分枝杆菌感染诱导的胸腺萎缩中起着重要作用。我们的研究结果表明，播散性感染的高致病力菌株的M。禽流感病毒，但不是与低毒力菌株，导致进行性胸腺萎缩。在不能产生IFNγ或诱导型一氧化氮合酶的遗传操作小鼠中，胸腺退化被阻止。此外，巨噬细胞中IFNγ信号传导选择性受损的小鼠同样受到感染诱导的胸腺萎缩的保护。皮质酮的浓度略有增加，发现在感染了高毒力菌株和胸腺细胞地塞米松诱导的死亡在播散性感染的易感性增加的小鼠。糖皮质激素受体拮抗剂的管理部分逆转感染引起的胸腺萎缩。我们观察到减少所有胸腺细胞群分析，包括最早的胸腺前体，表明胸腺殖民期间的T细胞前体和/或这些细胞在骨髓中的分化除了局部死亡的胸腺细胞的缺陷。我们的数据表明，在感染M.在局部产生的一氧化氮、内源性皮质类固醇活性和减少的骨髓接种的参与下，
Thymic atrophy has been described as a consequence of infection by several pathogens and shown to be induced through diverse mechanisms. Using the mouse model of Mycobacterium avium infection we show here that the production of nitric oxide from IFNγ-activated macrophages plays a major role in mycobacterial infection-induced thymic atrophy. Our results show that disseminated infection with a highly virulent strain of M. avium, but not with a low virulence strain, led to a progressive thymic atrophy. Thymic involution was prevented in genetically manipulated mice unable to produce IFNγ or the inducible nitric oxide synthase. In addition, mice with a selective impairment of IFNγ signaling in macrophages were similarly protected from infection-induced thymic atrophy. A slight increase in the concentration of corticosterone was found in mice infected with the highly virulent strain and thymocytes presented an increased susceptibility to dexamethasone-induced death during disseminated infection. The administration of an antagonist of glucocorticoid receptors partially reverted the infection-induced thymic atrophy. We observed a reduction in all thymocyte populations analyzed, including the earliest thymic precursors, suggesting a defect during thymic colonization by T cell precursors and/or during the differentiation of these cells in the bone-marrow in addition to local demise of thymic cells. Our data suggest a complex picture underlying thymic atrophy during infection by M. avium with the participation of locally produced nitric oxide, endogenous corticosteroid activity and reduced bone marrow seeding.
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胸腺和最近的胸腺移民在维持成年外周淋巴细胞库中的作用。
影响因子：
15.3
作者：
Berzins, S P;Boyd, R L;Miller, J F
通讯作者：
Miller, J F
DOI：
10.1073/pnas.96.17.9787
发表时间：
1999-08-17
影响因子：
11.1
作者：
Berzins, SP;Godfrey, DI;Boyd, RL
通讯作者：
Boyd, RL
影响因子：
3.3
作者：
DOBBS, CM;VASQUEZ, M;SHERIDAN, JF
通讯作者：
SHERIDAN, JF
影响因子：
20.3
作者：
de Bruin, Alexander M.;Libregts, Sten F.;Nolte, Martijn A.
通讯作者：
Nolte, Martijn A.
影响因子：
4.3
作者：
CHUNG, HT;SAMLOWSKI, WE;DAYNES, RA
通讯作者：
DAYNES, RA