Lipid‐associated membrane proteins of Mycoplasma fermentans and M. penetrans activate human immunodeficiency virus long‐terminal repeats through Toll‐like receptors
Lipid‐associated membrane proteins of Mycoplasma fermentans and M. penetrans activate human immunodeficiency virus long‐terminal repeats through Toll‐like receptors
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DOI：
10.1111/j.1365-2567.2004.01937.x
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发表时间：
2004-09
期刊：
影响因子：
6.4
通讯作者：
Takashi Shimizu;Yutaka Kida;K. Kuwano
中科院分区：
文献类型：
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作者：
Takashi Shimizu;Yutaka Kida;K. Kuwano
已知支原体可增强人类免疫缺陷病毒（HIV）的复制，据报道支原体衍生脂质提取物可通过Toll样受体（TLR）激活核因子-κB（NF-κB）。在这项研究中，我们检查了TLR参与支原体激活HIV长末端重复序列（LTR）及其负责TLR激活的活性组分。来自两种支原体（发酵支原体和支原体）的脂质相关膜蛋白（LAMP）。发现与获得性免疫缺陷综合征（AIDS）相关的抗HIV抗体（抗HIV抗体）可激活人单核细胞系THP-1中的HIV LTR。从LTR中删除NF-κB可抑制活化。M. TLR 1和TLR 6的显性负性（DN）结构抑制发酵菌LAMPs的表达，而M. DN TLR 1可抑制β-trans-LAMPs，但DN TLR 6不抑制β-trans-LAMPs。这些结果表明，M. fermentans和M. M. ltrans-LAMPs依赖于NF-κB，M.发酵菌的LAMPs通过TLR 1、TLR 2和TLR 6介导。相反，M.双反式LAMP通过TLR 1和TLR 2进行，但不通过TLR 6进行。随后，M.反枝霉M.通过反相高效液相色谱法（HPLC）纯化发酵菌LAMP。有趣的是，M. penetrans LAMPs（LPMp）能够通过TLR 1和TLR 2激活NF-κB。另一方面，纯化的M. LPMf是通过TLR 2和TLR 6介导的，而不是TLR 1。
Mycoplasmas are known to enhance human immunodeficiency virus (HIV) replication, and mycoplasma‐derived lipid extracts have been reported to activate nuclear factor‐κB (NF‐κB) through Toll‐like receptors (TLRs). In this study, we examined the involvement of TLRs in the activation of HIV long‐terminal repeats (LTR) by mycoplasma and their active components responsible for the TLR activation. Lipid‐associated membrane proteins (LAMPs) from two species of mycoplasma (Mycoplasma fermentans and M. penetrans) that are associated with acquired immune‐deficiency syndrome (AIDS), were found to activate HIV LTRs in a human monocytic cell line, THP‐1. NF‐κB deletion from the LTR resulted in inhibition of the activation. The LTR activation by M. fermentans LAMPs was inhibited by a dominant negative (DN) construct of TLR1 and TLR6, whereas HIV LTR activation by M. penetrans LAMPs was inhibited by DN TLR1, but not by DN TLR6. These results indicate that the activation of HIV LTRs by M. fermentans and M. penetrans LAMPs is dependent on NF‐κB, and that the activation of HIV LTR by M. fermentans LAMPs is mediated through TLR1, TLR2 and TLR6. In contrast, the LTR activation by M. penetrans LAMPs is carried out through TLR1 and TLR2, but not TLR6. Subsequently, the active component of M. penetrans and M. fermentans LAMPs was purified by reverse‐phase high‐performance liquid chromatography (HPLC). Interestingly, the purified lipoprotein of M. penetrans LAMPs (LPMp) was able to activate NF‐κB through TLR1 and TLR2. On the other hand, the activation of NF‐κB by purified lipoprotein of M. fermentans LAMPs (LPMf) was mediated through TLR2 and TLR6, but not TLR1.