...
首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Increased inflammation and impaired resistance to Chlamydophila pneumoniae infection in Dusp1a?’/a?’ mice: critical role of IL-6
【24h】

Increased inflammation and impaired resistance to Chlamydophila pneumoniae infection in Dusp1a?’/a?’ mice: critical role of IL-6

机译:在Dusp1a?/ a?'小鼠中炎症增加和对肺炎衣原体感染的抵抗力减弱:IL-6的关键作用

获取原文
           

摘要

The MAPK phosphatase DUSP1 is an essential negative regulator of TLR-triggered innate immune activation. Here, we have investigated the impact of DUSP1 on inflammatory and antimicrobial host responses to the intracellular pathogen Chlamydophila pneumoniae. Following nasal infection, DUSP1-deficient mice mounted an enhanced pulmonary cytokine (IL-1?2, IL-6) and chemokine response (CCL3, CCL4, CXCL1, CXCL2), leading to increased leukocyte infiltration. Of interest, the increased inflammatory response, in the absence of DUSP1, was associated with higher bacterial numbers in the lungs, although the expression of IFN-?3 and critical antichlamydial effector molecules, such as iNOS, was intact. Blockade of IL-6 trans-signaling by injection of a soluble gp130-Fc fusion protein corrected the overshooting chemokine production as well as the increased chlamydial load in Dusp1a?’/a?’ mice. Furthermore, IL-6 enhanced the replication of C. pneumoniae in embryonic fibroblasts in vitro. These data show that DUSP1 is required to achieve a balanced response to chlamydial infection and identify IL-6 as critical for amplifying inflammation and benefiting chlamydial growth through direct effects on infected cells.
机译:MAPK磷酸酶DUSP1是TLR触发的先天免疫激活的重要负调节剂。在这里,我们研究了DUSP1对细胞内病原体肺炎衣原体肺炎的炎症和抗菌宿主反应的影响。鼻腔感染后,DUSP1缺陷型小鼠的肺细胞因子(IL-1?2,IL-6)和趋化因子反应(CCL3,CCL4,CXCL1,CXCL2)增强,导致白细胞浸润增加。有趣的是,在没有DUSP1的情况下,炎症反应增加与肺中细菌数量增加有关,尽管IFN-α3和关键抗衣原体效应分子(如iNOS)的表达是完整的。通过注射可溶性gp130-Fc融合蛋白来阻断IL-6反信号,可以纠正Dusp1a?/ a?小鼠体内趋化因子的产生以及衣原体负荷的增加。此外,IL-6在体外增强了肺炎衣原体在胚胎成纤维细胞中的复制。这些数据表明,DUSP1是获得对衣原体感染的平衡反应所必需的,并将IL-6确定为通过直接作用于感染细胞来扩大炎症反应和促进衣原体生长的关键。

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号