Akt-mediated proinflammatory response of mononuclear phagocytes infected with Burkholderia cenocepacia occurs by a novel GSK3β-dependent, IκB kinase-independent mechanism.
Akt-mediated proinflammatory response of mononuclear phagocytes infected with Burkholderia cenocepacia occurs by a novel GSK3β-dependent, IκB kinase-independent mechanism.
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DOI：
10.4049/jimmunol.1003034
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发表时间：
2011-07-15
期刊：
影响因子：
--
通讯作者：
Tridandapani S
中科院分区：
文献类型：
--
作者：
Cremer TJ;Shah P;Cormet-Boyaka E;Valvano MA;Butchar JP;Tridandapani S
环境细菌新洋葱伯克霍尔德氏菌可导致免疫功能低下个体的机会性肺部感染，特别是囊性纤维化患者。这些患者的感染与炎症加剧有关，导致肺功能迅速衰退，在某些情况下导致洋葱综合征，其特征是致命的急性坏死性肺炎和败血症。B。新洋葱虫可通过改变吞噬体的成熟而在巨噬细胞内存活，但对巨噬细胞对细胞内感染的反应知之甚少。在这里，我们研究了PI 3 K/Akt信号通路在B中的作用。感染的单核细胞和巨噬细胞。我们发现，在B感染过程中，NF-κB B活性和促炎细胞因子的分泌需要PI 3 K/Akt活性。cenocepacia。与之前在感染其他革兰氏阴性菌的上皮细胞中观察到的结果相反，Akt不增强IKK或NF-κB p65磷酸化，而是抑制NF-κB转录活性的负调节因子GSK 3 β。这种调节NF-κB活性的新机制可能为控制B过度炎症提供独特的治疗靶点。新洋葱感染
The environmental bacterium Burkholderia cenocepacia causes opportunistic lung infections in immunocompromised individuals, particularly in patients with cystic fibrosis. Infections in these patients are associated with exacerbated inflammation leading to rapid decay of lung function and in some cases resulting in cepacia syndrome, which is characterized by a fatal acute necrotizing pneumonia and sepsis. B. cenocepacia can survive intracellularly in macrophages by altering the maturation of the phagosome, but very little is known on macrophage responses to the intracellular infection. Here, we have examined the role of the PI3K/Akt signaling pathway in B. cenocepacia-infected monocytes and macrophages. We show that PI3K/Akt activity was required for NF-κB activity and the secretion of pro-inflammatory cytokines during infection with B. cenocepacia. In contrast to previous observations in epithelial cells infected with other Gram-negative bacteria, Akt did not enhance IKK or NF-κB p65 phosphorylation but rather inhibited GSK3β, a negative regulator of NF-κB transcriptional activity. This novel mechanism of modulation of NF-κB activity may provide a unique therapeutic target for controlling excessive inflammation upon B. cenocepacia infection.
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