Toll-like receptors expression and interferon-γ production by NK cells in human sepsis.
Toll-like receptors expression and interferon-γ production by NK cells in human sepsis.
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DOI：
10.1186/cc11838
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发表时间：
2012-10-25
期刊：
影响因子：
--
通讯作者：
Captain study group
中科院分区：
文献类型：
--
作者：
Souza-Fonseca-Guimaraes F;Parlato M;Philippart F;Misset B;Cavaillon JM;Adib-Conquy M;Captain study group
在感染过程中，自然杀伤（NK）细胞通过产生细胞因子，特别是干扰素-γ（IFN-γ），促进先天免疫。除了它们对感染的有益作用之外，NK细胞可能在全身性炎症期间起有害作用，在脓毒症期间引起致死性。关于系统性炎症反应综合征（SIRS）或脓毒症患者NK细胞的免疫状态，在细胞表面标志物表达和IFN-γ产生方面知之甚少。我们研究了27例脓毒症患者和11例非感染性SIRS患者。通过流式细胞术鉴定CD 56 bright和CD 56 dim NK细胞亚群，并分析Toll样受体（TLR）2、TLR 4、TLR 9、CX 3CR 1、CD 16和CD 69表达，以及全血样品中NK细胞的离体IFN-γ产生。我们首先表明，在来自健康对照的NK细胞中，TLR 2和TLR 4表达主要是细胞内的，与TLR 9类似。与健康受试者相比，脓毒症患者的CD 56 bright和CD 56 dim NK细胞亚群中的细胞内TLR 2和TLR 4水平均升高。此外，脓毒症患者NK细胞中CD 69+细胞比例较高。TLR 9、CX 3CR 1和CD 16表达无差异。通过TLR 4或TLR 9激动剂或与辅助细胞因子（IL-15+IL-18）协同的全细菌的离体刺激导致健康对照的NK细胞显著产生IFN-γ。相反，对于SIRS和脓毒症患者，这种反应显著降低。本研究首次报道了TLR 2和TLR 4在人NK细胞中的细胞内表达。表面TLR 4表达允许区分脓毒症和SIRS。此外，在这些病理过程中，NK细胞经历其免疫状态的改变，其特征在于其释放IFN-γ的能力显著降低。
During the course of infection, natural killer (NK) cells contribute to innate immunity by producing cytokines, particularly interferon-gamma (IFN-γ). In addition to their beneficial effects against infection, NK cells may play a detrimental role during systemic inflammation, causing lethality during sepsis. Little is known on the immune status of NK cells in patients with systemic inflammatory response syndrome (SIRS) or sepsis in terms of cell surface markers expression and IFN-γ production. We investigated 27 sepsis patients and 11 patients with non-infectious SIRS. CD56bright and CD56dim NK cell subsets were identified by flow cytometry and Toll-like receptor (TLR)2, TLR4, TLR9, CX3CR1, CD16 and CD69 expression were analyzed, as well as ex vivo IFN-γ production by NK cells in whole blood samples. We first showed that in NK cells from healthy controls, TLR2 and TLR4 expression is mainly intracellular, similarly to TLR9. Intracellular levels of TLR2 and TLR4, in both CD56bright and CD56dim NK cell subsets from sepsis patients, were increased compared to healthy subjects. In addition, the percentage of CD69+ cells was higher among NK cells of sepsis patients. No difference was observed for TLR9, CX3CR1, and CD16 expression. The ex vivo stimulation by TLR4 or TLR9 agonists, or whole bacteria in synergy with accessory cytokines (IL-15+IL-18), resulted in significant production of IFN-γ by NK cells of healthy controls. In contrast, for SIRS and sepsis patients this response was dramatically reduced. This study reports for the first time an intracellular expression of TLR2 and TLR4 in human NK cells. Surface TLR4 expression allows discriminating sepsis and SIRS. Furthermore, during these pathologies, NK cells undergo an alteration of their immune status characterized by a profound reduction of their capacity to release IFN-γ.
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DOI：
10.1186/cc5055
发表时间：
2006
期刊：
Critical care (London, England)
影响因子：
--
作者：
Cavaillon JM;Adib-Conquy M
通讯作者：
Adib-Conquy M
影响因子：
120.7
作者：
Boomer, Jonathan S.;To, Kathleen;Chang, Kathy C.;Takasu, Osamu;Osborne, Dale F.;Walton, Andrew H.;Bricker, Traci L.;Jarman, Stephen D., II;Kreisel, Daniel;Krupnick, Alexander S.;Srivastava, Anil;Swanson, Paul E.;Green, Jonathan M.;Hotchkiss, Richard S.
通讯作者：
Hotchkiss, Richard S.
影响因子：
14.2
作者：
Holub, M;Klucková, Z;Beran, O
通讯作者：
Beran, O
Toll样受体4位于高尔基体中，并与肠上皮细胞中的内部脂多糖共定位。
DOI：
10.1084/jem.20011788
发表时间：
2002-03-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hornef MW;Frisan T;Vandewalle A;Normark S;Richter-Dahlfors A
通讯作者：
Richter-Dahlfors A
影响因子：
3
作者：
Hiraki, Shuhichi;Ono, Satoshi;Mochizuki, Hidetaka
通讯作者：
Mochizuki, Hidetaka