Natural killer cell cytokine response to M. bovis BCG Is associated with inhibited proliferation, increased apoptosis and ultimate depletion of NKp44(+)CD56(bright) cells.
Natural killer cell cytokine response to M. bovis BCG Is associated with inhibited proliferation, increased apoptosis and ultimate depletion of NKp44(+)CD56(bright) cells.
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DOI：
10.1371/journal.pone.0068864
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Young D
中科院分区：
文献类型：
--
作者：
Portevin D;Young D
牛分枝杆菌卡介苗是一种牛分枝杆菌的减毒活菌株，最初是作为结核病疫苗开发的，也被用作癌症免疫治疗和寄生虫感染治疗的佐剂。其潜在的机制被认为依赖于其免疫调节特性，包括招募自然杀伤(NK)细胞。在此背景下，我们的目的是研究卡介苗对NK细胞功能的影响。我们观察了单个分枝杆菌活颗粒暴露后纯化的人类NK细胞的细胞毒性、细胞因子产生、增殖和细胞存活。我们发现，卡介苗只有在IL-2刺激的情况下才能介导NK细胞的凋亡，在此过程中，CD56bright的NK细胞正在释放干扰素-γ以响应分枝杆菌。我们发现，分枝杆菌的存在阻止了IL-2诱导的细胞增殖和CD56bright群体表面NKp44受体的表达。总之，我们观察到卡介苗正在调节CD56bright NK细胞的功能，以在随后的细胞程序性死亡之前驱动这一亚群产生干扰素-γ。因此，CD56bright细胞产生的干扰素-γ构成了NK细胞的主要效应机制，有助于观察到卡介苗作为免疫治疗剂的益处。
Mycobacterium bovis BCG, a live attenuated strain of M. bovis initially developed as a vaccine against tuberculosis, is also used as an adjuvant for immunotherapy of cancers and for treatment of parasitic infections. The underlying mechanisms are thought to rely on its immunomodulatory properties including the recruitment of natural killer (NK) cells. In that context, we aimed to study the impact of M. bovis BCG on NK cell functions. We looked at cytotoxicity, cytokine production, proliferation and cell survival of purified human NK cells following exposure to single live particles of mycobacteria. We found that M. bovis BCG mediates apoptosis of NK cells only in the context of IL-2 stimulation during which CD56bright NK cells are releasing IFN-γ in response to mycobacteria. We found that the presence of mycobacteria prevented the IL-2 induced proliferation and surface expression of NKp44 receptor by the CD56bright population. In summary, we observed that M. bovis BCG is modulating the functions of CD56bright NK cells to drive this subset to produce IFN-γ before subsequent programmed cell death. Therefore, IFN-γ production by CD56bright cells constitutes the main effector mechanism of NK cells that would contribute to the benefits observed for M. bovis BCG as an immunotherapeutic agent.
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影响因子：
3.1
作者：
Brandt, L;Cunha, JF;Andersen, P
通讯作者：
Andersen, P
影响因子：
3.4
作者：
Portevin D;Via LE;Eum S;Young D
通讯作者：
Young D
影响因子：
20.3
作者：
Fauriat, Cyril;Long, Eric O.;Bryceson, Yenan T.
通讯作者：
Bryceson, Yenan T.
影响因子：
4.4
作者：
Marcenaro, Emanuela;Ferranti, Bruna;Moretta, Alessandro
通讯作者：
Moretta, Alessandro
影响因子：
4.4
作者：
Feng, Carl G.;Kaviratne, Mallika;Sher, Alan
通讯作者：
Sher, Alan