Chlamydia muridarum infection elicits a beta interferon response in murine oviduct epithelial cells dependent on interferon regulatory factor 3 and TRIF
Chlamydia muridarum infection elicits a beta interferon response in murine oviduct epithelial cells dependent on interferon regulatory factor 3 and TRIF
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DOI：
10.1128/iai.01525-06
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发表时间：
2007-03-01
影响因子：
3.1
通讯作者：
Johnson, Raymond M.
中科院分区：
文献类型：
--
作者：
Derbigny, Wilbert A.;Hong, Soon-Cheol;Johnson, Raymond M.
沙眼衣原体是美国最常见的性传播细菌感染。利用克隆的小鼠输卵管上皮细胞系，我们以前确定Toll样受体2（TLR 2）作为主要的上皮模式识别受体，（PRR）感染触发释放的急性炎症细胞因子白细胞介素-6和粒细胞-巨噬细胞集落刺激因子。感染的输卵管上皮细胞系也分泌免疫调节细胞因子β干扰素（IFN-β）在很大程度上MyD 88独立的方式。尽管TLR 3是输卵管细胞系表达的唯一能够产生IFN-β的TLR，但我们不能确定TLR 3是否负责IFN-β的产生，因为上皮细胞对TLR 3配体poly（I-C）无反应，并且小干扰RNA（siRNA）技术在敲低TLR 3表达方面无效。为了进一步研究TLR 3在受感染的上皮细胞分泌IFN-β中的潜在作用，我们使用显性负性TRIF分子和TRIF和IRF-3特异性siRNA检测了其下游信号分子TRIF和IFN调节因子3（IRF-3）的作用。IRF-3或TRIF信号传导的拮抗显著降低IFN-β产生。这些数据暗示TLR 3或利用TRIF的未知PRR是衣原体感染的输卵管上皮细胞产生IFN-β的来源。
Chlamydia trachomatis is the most common sexually transmitted bacterial infection in the United States. Utilizing cloned murine oviduct epithelial cell lines, we previously identified Toll-like receptor 2 (TLR2) as the principal epithelial pattern recognition receptor, (PRR) for infection-triggered release of the acute inflammatory cytokines interleukin-6 and granulocyte-macrophage colony-stimulating factor. The infected oviduct epithelial cell lines also secreted the immunomodulatory cytokine beta interferon (IFN-beta) in a largely MyD88-independent manner. Although TLR3 was the only IFN-beta production-capable TLR expressed by the oviduct cell lines, we were not able to determine whether TLR3 was responsible for IFN-beta production because the epithelial cells were unresponsive to the TLR3 ligand poly(I-C), and small interfering RNA (siRNA) techniques were ineffective at knocking down TLR3 expression. To further investigate the potential role of TLR3 in the infected epithelial cell secretion of IFN-beta, we examined the roles of its downstream signaling molecules TRIF and IFN regulatory factor 3 (IRF-3) using a dominant-negative TRIF molecule and siRNA specific for TRIF and IRF-3. Antagonism of either IRF-3 or TRIF signaling significantly decreased IFN-beta production. These data implicate TLR3, or an unknown PRR utilizing TRIF, as the source of IFN-beta production by Chlamydia-infected oviduct epithelial cells.