The T cell STAT signaling network is reprogrammed within hours of bacteremia via secondary signals.
The T cell STAT signaling network is reprogrammed within hours of bacteremia via secondary signals.
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T 细胞 STAT 信号网络在菌血症发生后数小时内通过次级信号重新编程。
DOI：
10.4049/jimmunol.0803666
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发表时间：
2009-06-15
期刊：
影响因子：
--
通讯作者：
Nolan GP
中科院分区：
文献类型：
--
作者：
Hotson AN;Hardy JW;Hale MB;Contag CH;Nolan GP
在脓毒症期间，保护性免疫和炎性疾病之间的微妙平衡受到挑战，脓毒症是一种以过度活跃的免疫应答和免疫抑制两方面为特征的病理状态。可能控制这些反应的T细胞信号传导网络上的细菌病原体的全身感染驱动的事件尚未详细说明。我们表征了当宿主受到高水平病原体的挑战时，免疫区室内的细胞内信号传导如何在单细胞水平上重新编程。为了实现这一点，我们应用流式细胞术来测量在急性细菌挑战期间关键信号转导蛋白的磷酸化潜力。我们通过静脉注射李斯特菌和大肠杆菌的无毒菌株来模拟脓毒症的发作。coli感染小鼠。在细菌攻击的6小时内，T细胞对特异性细胞因子刺激的反应能力全面受限，如通过评估STAT蛋白磷酸化程度所确定的。这种负反馈反应发生的机制包括SOCS 1和SOCS 3基因上调和IL-6诱导的IL-6受体的内吞。此外，巨噬细胞对TLR激动剂的反应能力部分耐受。因此，与脓毒症期间存在大规模免疫激活的观点相反，对血源性细菌的一种直接宿主反应是诱导不应期，在此期间特异性刺激引起的白细胞激活减弱。
The delicate balance between protective immunity and inflammatory disease is challenged during sepsis, a pathologic state characterized by aspects of both a hyper-active immune response and immunosuppression. The events driven by systemic infection by bacterial pathogens on the T cell signaling network that likely control these responses have not been illustrated in great detail. We characterized how intracellular signaling within the immune compartment is reprogrammed at the single cell level when the host is challenged with a high levels of pathogen. To accomplish this, we applied flow cytometry to measure the phosphorylation potential of key signal transduction proteins during acute bacterial challenge. We modeled the onset of sepsis by intravenous administration of avirulent strains of Listeria and E. coli to mice. Within six hours of bacterial challenge, T cells were globally restricted in their ability to respond to specific cytokine stimulations as determined by assessing the extent of STAT protein phosphorylation. Mechanisms by which this negative feedback response occurred included SOCS1 and SOCS3 gene up regulation and IL-6 induced endocystosis of the IL-6 receptor. In addition, macrophages were partially tolerized in their ability to respond to TLR agonists. Thus, in contrast to the view that there is a wholesale immune activation during sepsis, one immediate host response to blood borne bacteria was induction of a refractory period during which leukocyte activation by specific stimulations was attenuated.
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DOI：
10.1084/jem.20081571
发表时间：
2009-01-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dienz O;Eaton SM;Bond JP;Neveu W;Moquin D;Noubade R;Briso EM;Charland C;Leonard WJ;Ciliberto G;Teuscher C;Haynes L;Rincon M
通讯作者：
Rincon M
适应性免疫细胞缓和最初的先天反应。
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
20.3
作者：
Eddahri, Fouad;Denanglaire, Sebastien;Andris, Fabienne
通讯作者：
Andris, Fabienne
影响因子：
3.5
作者：
Bode, JG;Nimmesgern, A;Graeve, L
通讯作者：
Graeve, L
影响因子：
3.2
作者：
BERRY, LJ;SMYTHE, DS
通讯作者：
SMYTHE, DS