Overexpression of Toll-like receptor 4 enhances LPS-induced inflammatory response and inhibits Salmonella Typhimurium growth in ovine macrophages

文献类型： 外文期刊

第一作者： Fu, Juncai

作者： Fu, Juncai;Wei, Shao;Yang, Dongbing;Yang, Jifan;Lian, Zhengxing;Han, Hongbing;Wei, Shao;Yang, Dongbing;Lian, Zhengxing;Han, Hongbing;Zhang, Xiaosheng;Zhang, Jinlong;Liu, Haijun;Zhou, Guangbin

作者机构：

关键词： Ovine macrophage; Overexpression TLR4; IRAK4; TBK1; Salmonella

期刊名称：EUROPEAN JOURNAL OF CELL BIOLOGY （ 影响因子：4.492； 五年影响因子：3.807 ）

ISSN： 0171-9335

年卷期： 2019 年 98 卷 1 期

页码：

收录情况： SCI

摘要： The Toll-like receptor 4 (TLR4) plays a crucial role in innate inflammatory responses, as it recognizes gram-negative bacteria (or their products) and contributes greatly to host defense against invading pathogens. Though TLR4 overexpressing transgenic sheep, resistant to certain diseases related with gram-negative bacteria, had been bred in our previous research, the effects of overexpression of TLR4 on innate immune response remained unclear. In this study, TLR4 overexpressing ovine macrophages were obtained from peripheral blood, and it was found that the overexpression of TLR4 initially promoted the production of proinflammatory cytokines TNF alpha and IL-6 by activating TLR4-mediated IRAK4-dependent NF-kappa B and MAPK (JNK and ERK1/2) signaling following LPS stimulation. However, this effect was later impaired due to increased internalization of TLR4 into endosomal compartment of the macrophages. Then the overexpression of TLR4 triggered TBK1-dependent interferon-regulatory factor-3 (IRF-3) expression, which in turn led to the induction of IFN-beta and IFN-inducible genes (i.e.IP10, IRG1 and GARG16). Understandably, an increased IFN-beta level facilitated phosphorylation of STAT1 to induce expression of innate antiviral genes Mx1 and ISG15, suggesting that TLR4 overexpressing macrophages were equipped better against viral infection. Correspondingly, the bacterial burden in these macrophages, after infection with live S. Typhimurium, was decreased significantly. In summary, the results indicated that overexpression of TLR4 could enhance innate inflammatory responses, initiate the innate antiviral immunity, and control effectively S. Typhimurium growth in ovine macrophages.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序