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首页> 外文期刊>Cytokine >Mycobacterium tuberculosis ESAT6 induces IFN-beta gene expression in Macrophages via TLRs-mediated signaling
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Mycobacterium tuberculosis ESAT6 induces IFN-beta gene expression in Macrophages via TLRs-mediated signaling

机译：结核分枝杆菌eSat6通过TLRS介导的信号传导诱导巨噬细胞中的IFN-β基因表达

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摘要

Mycobacterium tuberculosis is a highly virulent bacterium that causes tuberculosis. It infects about one third of the world's population. Type I interferons (IFNs) play a detrimental role in host defense against M. tuberculosis infection. Proteins secreted by M. tuberculosis through ESX-1 secretion system contribute to type I IFNs production. However, the precise mechanism by which 6-kDa early secretory antigen target (ESAT6), one of ESX-1-mediated secretory proteins, induces type I IFNs production in host cells is currently unclear. Therefore, the objective of the present study was to determine the underlying molecular mechanism regulating ESAT6-mediated gene expression of IFN-beta in macrophages. Recombinant ESAT6 produced from E. coli expression system induced IFN-beta gene expression in various types of macrophages such as mouse bone marrow-derived macrophages (BMDMs), peritoneal macrophages, and MH-S cells (murine alveolar macrophage cell line). Deficiency of TLR4- and TRIF absolutely abrogated ESAT6-induced IFN-beta gene expression. TLR2 and MyD88 were partially involved in IFN-beta gene expression in response to low dose of ESAT6. Another recombinant ESAT6 produced from baculovirus system also upregulated IFN-beta gene expression via TLR4-dependent pathway. Polymyxin B (PMB) treatment impaired LPS-induced IFN-beta expression. However, IFN-beta expression induced by ESAT6 was not influenced by PMB. This suggests that ESAT6-mediated IFN-beta expression is not due to LPS contamination. Treatment with ESAT6 resulted in activation of TBK1 and IRF3 in macrophages. Such activation was abolished in TLR4- and TRIF-deficient cells. Moreover, inhibition of IRF3 and TBK1 suppressed IFN-beta gene expression in response to ESAT6. Our results suggest that ESAT6 might contribute to virulence of M. tuberculosis by regulating type I IFNs production through TLR4-TRIF signaling pathway.
机译：结核分枝杆菌是一种高毒性的细菌，导致结核病。它感染了世界上三分之一的人口。 I型干扰素（IFNS）在宿主防御中发挥不利作用针对结核病感染。通过ESX-1分泌系统分泌的M.结核分泌的蛋白有助于I型IFNS生产。然而，通过其中6-KDA早期分泌抗原靶（ESAT6），ESX-1介导的分泌蛋白之一的精确机制目前不清楚。因此，本研究的目的是确定调节IFN-β中IFN-β的潜在分子机制的潜在分子机制。从大肠杆菌表达系统中产生的重组ESAT6在各种类型的巨噬细胞中诱导IFN-β基因表达，例如小鼠骨髓衍生的巨噬细胞（BMDMS），腹膜巨噬细胞和MH-S细胞（鼠肺泡巨噬细胞系）。 TLR4和TRIF的缺乏绝对废除ESAT6诱导的IFN-β基因表达。 TLR2和MYD88部分涉及IFN-β基因表达，响应于低剂量的ESAT6。由杆状病毒系统产生的另一种重组ESAT6也通过TLR4依赖性途径上调IFN-Beta基因表达。多粘菌素B（PMB）治疗损害LPS诱导的IFN-β表达。然而，ESAT6诱导的IFN-β表达不受PMB的影响。这表明ESAT6介导的IFN-β表达不是由于LPS污染。用ESAT6治疗导致巨噬细胞中的TBK1和IRF3活化。在TLR4和TRIF缺陷细胞中消除了这种活化。此外，抑制IRF3和TBK1抑制IFN-β基因表达响应于ESAT6。我们的研究结果表明，ESAT6可以通过通过TLR4-TRIF信号通路调节I IFNS产生来促进肺结核的毒力。

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  • 来源
    《Cytokine》 |2018年第2018期|共6页
  • 作者

    Jang Ah-Ra; Choi Joo-Hee; Shin Sung Jae; Park Jong-Hwan;

  • 作者单位

    Chonnam Natl Univ Coll Vet Med Lab Anim Med 77 Yongbong Ro Gwangju 61186 South Korea;

    Chonnam Natl Univ Coll Vet Med Lab Anim Med 77 Yongbong Ro Gwangju 61186 South Korea;

    Yonsei Univ Coll Med Brain Korea PLUS Project Med Sci 21 Dept Microbiol Inst Immunol &

    Immunol;

    Chonnam Natl Univ Coll Vet Med Lab Anim Med 77 Yongbong Ro Gwangju 61186 South Korea;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    Mycobacterium tuberculosis; ESAT6; IFN-beta; TLRs; Macrophages;

    机译：结核分枝杆菌;ESAT6;IFN-BETA;TLRS;巨噬细胞;

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