Analyses of the pathways involved in early- and late-phase induction of IFN-beta during C. muridarum infection of oviduct epithelial cells.
Analyses of the pathways involved in early- and late-phase induction of IFN-beta during C. muridarum infection of oviduct epithelial cells.
复制标题
DOI：
10.1371/journal.pone.0119235
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Derbigny WA
中科院分区：
文献类型：
--
作者：
Hu S;Hosey KL;Derbigny WA
我们先前报道，衣原体感染的小鼠输卵管上皮细胞(OE细胞)分泌的干扰素-β主要依赖于TLR3信号通路。为了进一步研究衣原体体外感染OE细胞过程中干扰素-β合成的机制，我们利用特异性的抑制药物来阐明IRF3和NF-κB在早期和晚期沙眼衣原体感染中的作用。我们的结果表明，干扰素-β产生的早期阶段所涉及的途径与干扰素-β产生的晚期阶段不同。在衣原体感染的早期用tbk-1的抑制剂阻断irf3的激活对干扰素-β的整体合成有显著的影响；然而，在感染的后期阻断irf3的激活没有影响。有趣的是，在衣原体感染早期抑制NF-κB对干扰素-β的产生也有负面影响，但其影响并不显著。我们的数据表明，转录因子irf7在衣原体感染后期被诱导，这表明在感染后期干扰素-β的合成是一种正反馈机制。相反，在衣原体感染的早期干扰素-β的合成中，irf7的作用似乎很小，甚至没有。最后，我们证明，与针对衣原体转录的抗生素相比，针对衣原体复制的抗生素在减少感染期间干扰素-β合成方面要有效得多。这些结果提供了证据，表明在衣原体感染的OE细胞中，早期和晚期产生干扰素-β具有不同的信号通路，并提示衣原体DNA复制可能提供了与目前未知的衣原体TLR3PAMP的联系。
We previously reported that the IFN-β secreted by Chlamydia muridarum-infected murine oviduct epithelial cells (OE cells) was mostly dependent on the TLR3 signaling pathway. To further characterize the mechanisms of IFN-β synthesis during Chlamydia infection of OE cells in vitro, we utilized specific inhibitory drugs to clarify the roles of IRF3 and NF-κB on both early- and late-phase C. muridarum infections. Our results showed that the pathways involved in the early-phase of IFN-β production were distinct from that in the late-phase of IFN-β production. Disruption of IRF3 activation using an inhibitor of TBK-1 at early-phase Chlamydia infection had a significant impact on the overall synthesis of IFN-β; however, disruption of IRF3 activation at late times during infection had no effect. Interestingly, inhibition of NF-κB early during Chlamydia infection also had a negative effect on IFN-β production; however, its impact was not significant. Our data show that the transcription factor IRF7 was induced late during Chlamydia infection, which is indicative of a positive feedback mechanism of IFN-β synthesis late during infection. In contrast, IRF7 appears to play little or no role in the early synthesis of IFN-β during Chlamydia infection. Finally, we demonstrate that antibiotics that target chlamydial DNA replication are much more effective at reducing IFN-β synthesis during infection versus antibiotics that target chlamydial transcription. These results provide evidence that early- and late-phase IFN-β production have distinct signaling pathways in Chlamydia-infected OE cells, and suggest that Chlamydia DNA replication might provide a link to the currently unknown chlamydial PAMP for TLR3.
登录
查看更多内容
影响因子：
3.1
作者：
Devitt, A;Lund, PA;Pearce, JH
通讯作者：
Pearce, JH
I型Interferon自分泌 - 核酸环与树突状细胞的Toll样受体诱导的白介素-12p70分泌有关。
影响因子：
15.3
作者：
Gautier, G;Humbert, M;Deauvieau, F;Scuiller, M;Hiscott, J;Bates, EEM;Trinchieri, G;Caux, C;Garrone, P
通讯作者：
Garrone, P
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
DOI：
10.4049/jimmunol.181.10.7186
发表时间：
2008-11-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Chen S;Sorrentino R;Shimada K;Bulut Y;Doherty TM;Crother TR;Arditi M
通讯作者：
Arditi M
影响因子：
15.9
作者：
Kagnoff, MF;Eckmann, L
通讯作者：
Eckmann, L