Dysfunction of Natural Killer T Cells in Patients with Active Mycobacterium tuberculosis Infection
Dysfunction of Natural Killer T Cells in Patients with Active Mycobacterium tuberculosis Infection
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DOI：
10.1128/iai.06018-11
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发表时间：
2012-06-01
影响因子：
3.1
通讯作者：
Ryang, Dong-Wook
中科院分区：
文献类型：
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作者：
Kee, Seung-Jung;Kwon, Yong-Soo;Ryang, Dong-Wook
已知自然杀伤T(NKT)细胞在小鼠对各种感染性病原体的免疫反应中发挥保护作用。然而，有关结核分枝杆菌感染患者NKT细胞的详细信息却知之甚少。本研究的目的是检测活动性结核分枝杆菌感染者的NKT细胞水平和功能，探讨NKT细胞水平与临床参数的关系，并确定对α-氨基半乳糖神经酰胺(α-GalCer)反应差的机制。肺结核和肺外结核患者外周血中NKT细胞水平显著降低，NKT细胞对α-GalCer的增殖反应也较低，而潜伏性结核感染者和健康对照组的NKT细胞水平和反应相似。此外，这种NKT细胞缺陷被发现与血清C反应蛋白水平有关。此外，结核分枝杆菌感染患者对α-GalCer的不良反应被发现是由于NKT细胞凋亡增加、CD1d表达减少以及NKT细胞缺陷所致。值得注意的是，结核分枝杆菌感染与NKT细胞上抑制性程序性死亡-1(PD-1)受体的表达增加有关，阻断PD-1信号增强了对α-GalCer的反应。这项研究表明，在结核分枝杆菌感染的患者中，NKT细胞水平和功能降低，这些缺陷被发现反映了活动性结核病的存在。
Natural killer T (NKT) cells are known to play a protective role in the immune responses of mice against a variety of infectious pathogens. However, little is known about the detailed information of NKT cells in patients with Mycobacterium tuberculosis infection. The aims of this study were to examine NKT cell levels and functions in patients with active M. tuberculosis infection, to investigate relationships between NKT cell levels and clinical parameters, and to determine the mechanism responsible for the poor response to alpha-galactosylceramide (alpha-GalCer). NKT cell levels were significantly lower in the peripheral blood of pulmonary tuberculosis and extrapulmonary tuberculosis patients, and the proliferative responses of NKT cells to alpha-GalCer were also lower in patients, whereas NKT cell levels and responses were comparable in latent tuberculosis infection subjects and healthy controls. Furthermore, this NKT cell deficiency was found to be correlated with serum C-reactive protein levels. In addition, the poor response to alpha-GalCer in M. tuberculosis-infected patients was found to be due to increased NKT cell apoptosis, reduced CD1d expression, and a defect in NKT cells. Notably, M. tuberculosis infection was associated with an elevated expression of the inhibitory programmed death-1 (PD-1) receptor on NKT cells, and blockade of PD-1 signaling enhanced the response to alpha-GalCer. This study shows that NKT cell levels and functions are reduced in M. tuberculosis-infected patients and these deficiencies were found to reflect the presence of active tuberculosis.