The cytosolic pattern recognition receptor NOD1 induces inflammatory interleukin-8 during Chlamydia trachomatis infection
The cytosolic pattern recognition receptor NOD1 induces inflammatory interleukin-8 during Chlamydia trachomatis infection
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DOI：
10.1128/iai.00104-08
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发表时间：
2008-07-01
影响因子：
3.1
通讯作者：
Stephens, Richard S.
中科院分区：
文献类型：
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作者：
Buchholz, Kerry R.;Stephens, Richard S.
炎症是衣原体感染的标志，但如何诱导炎症细胞因子尚不清楚。宿主先天免疫系统的模式识别受体（PRR）识别病原体分子并激活调节免疫反应的细胞内信号通路。 PRR（例如 Toll 样受体 (TLR) 和核苷酸结合寡聚结构域 (NOD) 蛋白）在沙眼衣原体感染期间诱导的内源性白细胞介素 8 (IL-8) 反应中的作用尚不清楚。我们假设 PRR 对于沙眼衣原体感染诱导的 IL-8 反应至关重要。 RNA 干扰用于敲低 TLR 信号传导伴侣 MyD88 以及 NODI 及其信号分子受体相互作用蛋白 2 (RIP2)。沙眼衣原体感染后 30 小时诱导的 IL-8 依赖于通过 RIP2 的 NODI 信号传导；然而，IL-8 反应独立于 MyD88 依赖性 TLR 信号传导。细胞外信号调节激酶 (ERK) 丝裂原激活蛋白激酶细胞信号通路的激活不依赖于 NOD1 或 RIP2，该信号通路对于响应沙眼衣原体感染而上调 IL-8 至关重要。我们得出的结论是，沙眼衣原体感染诱导的内源性 IL-8 反应依赖于通过 RIP2 的 NODI PRR 信号传导，作为需要多个输入以实现最佳 IL-8 诱导的信号系统的一部分。由于 ERK 不是通过该途径激活的，因此，为了完全激活内源性 IL-8 反应，还需要宿主和细菌之间伴随的相互作用。
Inflammation is a hallmark of chlamydial infections, but how inflammatory cytokines are induced is not well understood. Pattern recognition receptors (PRR) of the host innate immune system recognize pathogen molecules and activate intracellular signaling pathways that modulate immune responses. The role of PRR such as Toll-like receptors (TLR) and nucleotide-binding oligomerization domain (NOD) proteins in the endogenous interleukin-8 (IL-8) response induced during Chlamydia trachomatis infection is not known. We hypothesized that a PRR is essential for the IL-8 response induced by C trachomatis infection. RNA interference was used to knock down the TLR signaling partner MyD88 as well as NODI and its signaling molecule receptor-interacting protein 2 (RIP2). IL-8 induced at 30 h postinfection by C trachomatis was dependent on NODI signaling through RIP2; however, the IL-8 response was independent of MyD88-dependent TLR signaling. Activation of the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase cellular signaling pathway, which is essential for up-regulation of IL-8 in response to C trachomatis infection, was independent of NOD1 or RIP2. We conclude that the endogenous IL-8 response induced by C trachomatis infection is dependent upon NODI PRR signaling through RIP2 as part of a signal system requiring multiple inputs for optimal IL-8 induction. Since ERK is not activated through this pathway, a concomitant interaction between the host and bacteria is additionally required for full activation of the endogenous IL-8 response.