Toxoplasma gondii tachyzoites inhibit proinflammatory cytokine induction in infected macrophages by preventing nuclear translocation of the transcription factor NF-κB
Toxoplasma gondii tachyzoites inhibit proinflammatory cytokine induction in infected macrophages by preventing nuclear translocation of the transcription factor NF-κB
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DOI：
10.4049/jimmunol.167.4.2193
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发表时间：
2001-08-15
影响因子：
4.4
通讯作者：
Denkers, EY
中科院分区：
文献类型：
--
作者：
Butcher, BA;Kim, L;Denkers, EY
控制微生物感染需要有规律地诱导依赖于核因子-kappaB的促炎细胞因子，如IL-12和TNF-α。这个重要的转录因子的激活是由抑制的I kappaB分子的磷酸化依赖的降解驱动的，这一事件使NF-kappaB从细胞质转移到细胞核。在这项研究中，我们发现巨噬细胞内感染原生动物弓形虫可以诱导I-kappaB的快速磷酸化和降解。然而，核因子-kappaB未能转位到细胞核，使寄生虫能够入侵细胞，而不会触发促炎细胞因子的诱导。由于速殖子诱导阻断了核转录因子-kappaB的核转位，随后受到内毒素触发的感染细胞产生IL-12和肿瘤坏死因子-α的能力严重受损。我们的结果首次证明了细胞内原生动物能够主动干扰巨噬细胞中的核因子-kappaB激活途径。一种可使寄生虫在宿主内存活的活动。
Control of microbial infection requires regulated induction of NF-kappaB-dependent proinflammatory cytokines such as IL-12 and TNF-alpha. Activation of this important transcription factor is driven by phosphorylation-dependent degradation of the inhibitory I kappaB molecule, an event which enables NF-kappaB translocation from the cytoplasm to the nucleus. In this study, we show that intracellular infection of macrophages with the protozoan parasite Toxoplasma gondii induces rapid I kappaB phosphorylation and degradation. Nevertheless, NF-kappaB failed to translocate to the nucleus, enabling the parasite to invade cells without triggering proinflammatory cytokine induction. Infected cells subsequently subjected to LPS triggering were severely crippled in IL-12 and TNF-alpha production, a result of tachyzoite-induced blockade of NF-kappaB nuclear translocation. Our results are the first to demonstrate the ability of an intracellular protozoan to actively interfere with the NF-kappaB activation pathway in macrophages. an activity that may enable parasite survival within the host.