Functionally relevant decreases in activatory receptor expression on NK cells are associated with pulmonary tuberculosis in vivo and persist after successful treatment
Functionally relevant decreases in activatory receptor expression on NK cells are associated with pulmonary tuberculosis in vivo and persist after successful treatment
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DOI：
10.1093/intimm/dxp046
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发表时间：
2009-07-01
影响因子：
4.4
通讯作者：
De Maria, Andrea
中科院分区：
文献类型：
--
作者：
Bozzano, Federica;Costa, Paola;De Maria, Andrea
需要从潜伏期开始人结核菌（Mth）复制的相关因子，以改善其控制。为了分析外周NK细胞的扰动是否可能与m潜伏期的退出有关，我们对新诊断的肺结核（TB）患者进行了连续研究。采用细胞荧光法、体外培养法和功能法对外周血NK细胞进行分析。在肺结核发病时，NK细胞亚群的失衡是明显的。CD56（明亮）CD16（+/-）亚群明显减少，NKp30和NKp46表达显著受损，触发后γ - ifn产生特异性减少。纯化的NK细胞在体外培养时，这些特征没有完全恢复。在结核和健康供体中补充α - ifn仅增加NKp30的表达。在这些患者中，NK细胞激活标记物和淋巴结归巢趋化因子受体CCR7在CD16(+) CD56（暗）细胞上的表达表明，外周血NK细胞的广泛触发是明显的。在标准四药方案治疗成功后，在完全康复后检测到NKp30和NKp46的显著持续下降。NK细胞功能在肺结核发病时受到严重影响。多种激活受体的参与可能为潜伏期的分枝杆菌传播提供了相关的贡献。
Correlates for the initiation of Mycobacterium tuberculosis hominis (Mth) replication from latency are needed in order to improve Mth control. In order to analyze if perturbations of peripheral NK cells may be associated with exit from Mth latency, sequential patients with newly diagnosed lung tuberculosis (TB) were studied. Peripheral NK cells were analyzed by cytofluorometry, in vitro culture and functional assays. At the onset of lung TB, imbalances in NK cell subsets were evident. Decreased CD56(bright)CD16(+/-) subsets with significantly compromised NKp30 and NKp46 expression and with specifically decreased gamma-IFN production upon triggering were evident. These features were not completely restored when purified NK cells were cultured in vitro. Culture supplementation with alpha-IFN increased only NKp30 expression in TB and healthy donors. Extensive peripheral NK cell triggering was evident in these patients, as shown by the expression of NK cell activation markers and of the lymph node-homing chemokine receptor CCR7 on CD16(+) CD56(dull) cells. Significant persistence of decreased NKp30 and NKp46 after successful treatment with a standard four-drug regimen was detected after full recovery. NK cell function is deeply affected in patients at the onset of pulmonary TB. The involvement of multiple activatory receptors may provide a relevant contribution to the spread of mycobacteria exiting from latency.