• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>PLoS Pathogens >Impaired Innate Immunity in Tlr4−/− Mice but Preserved CD8+ T Cell Responses against Trypanosoma cruzi in Tlr4- Tlr2- Tlr9- or Myd88-Deficient Mice
【2h】

Impaired Innate Immunity in Tlr4−/− Mice but Preserved CD8+ T Cell Responses against Trypanosoma cruzi in Tlr4- Tlr2- Tlr9- or Myd88-Deficient Mice

机译：Tlr4的先天免疫力受损-/-小鼠但保留了针对Tlr4-Tlr2-Tlr9-或Myd88缺陷型小鼠的克氏锥虫的CD8 + T细胞应答

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The murine model of T. cruzi infection has provided compelling evidence that development of host resistance against intracellular protozoans critically depends on the activation of members of the Toll-like receptor (TLR) family via the MyD88 adaptor molecule. However, the possibility that TLR/MyD88 signaling pathways also control the induction of immunoprotective CD8+ T cell-mediated effector functions has not been investigated to date. We addressed this question by measuring the frequencies of IFN-γ secreting CD8+ T cells specific for H-2Kb-restricted immunodominant peptides as well as the in vivo Ag-specific cytotoxic response in infected animals that are deficient either in TLR2, TLR4, TLR9 or MyD88 signaling pathways. Strikingly, we found that T. cruzi-infected Tlr2−/−, Tlr4−/−, Tlr9−/ − or Myd88−/− mice generated both specific cytotoxic responses and IFN-γ secreting CD8+ T cells at levels comparable to WT mice, although the frequency of IFN-γ+CD4+ cells was diminished in infected Myd88−/− mice. We also analyzed the efficiency of TLR4-driven immune responses against T. cruzi using TLR4-deficient mice on the C57BL genetic background (B6 and B10). Our studies demonstrated that TLR4 signaling is required for optimal production of IFN-γ, TNF-α and nitric oxide (NO) in the spleen of infected animals and, as a consequence, Tlr4−/− mice display higher parasitemia levels. Collectively, our results indicate that TLR4, as well as previously shown for TLR2, TLR9 and MyD88, contributes to the innate immune response and, consequently, resistance in the acute phase of infection, although each of these pathways is not individually essential for the generation of class I-restricted responses against T. cruzi.
机译：克氏锥虫感染的小鼠模型提供了令人信服的证据，表明宿主对细胞内原生动物的抗性发展主要取决于通过MyD88衔接子分子激活Toll样受体（TLR）家族的成员。然而，迄今尚未研究TLR / MyD88信号通路也控制诱导免疫保护性CD8 + T细胞介导的效应子功能的可能性。我们通过测量对H-2K b 限制性免疫优势肽和体内Ag特异性肽的IFN-γ分泌CD8 + T细胞的频率来解决这个问题TLR2，TLR4，TLR9或MyD88信号通路不足的受感染动物的细胞毒性反应。令人惊讶的是，我们发现了被克鲁氏杆菌感染的Tlr2 -/-，Tlr4 -/-，Tlr9 -/ -或Myd88 -/-小鼠产生特定的细胞毒性反应和IFN-γ分泌CD8 + T细胞，其水平与WT小鼠相当，尽管IFN-γ的频率在感染的Myd88 -/-小鼠中， + CD4 + 细胞减少了。我们还分析了在C57BL遗传背景（B6和B10）上使用TLR4缺陷小鼠对T.cruz的TLR4驱动的免疫反应的效率。我们的研究表明，TLR4信号传导是感染动物脾脏中IFN-γ，TNF-α和一氧化氮（NO）最佳生成所必需的，因此，Tlr4 -/-小鼠展示较高的寄生虫血症水平。总体而言，我们的结果表明，TLR4以及先前针对TLR2，TLR9和MyD88的研究均有助于先天性免疫应答，因此也有助于感染急性期的耐药性，尽管这些途径中的每一个都不是世代必需的。一类限制了针对克鲁氏锥虫的反应。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

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