...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Infection and immunity >Mycobacterium tuberculosis Growth at the Cavity Surface: a Microenvironment with Failed Immunity
【24h】

Mycobacterium tuberculosis Growth at the Cavity Surface: a Microenvironment with Failed Immunity

机译：腔表面结核分枝杆菌的生长：免疫失败的微环境。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Protective immunity against pulmonary tuberculosis (TB) is characterized by the formation in the lungs of granulomas consisting of macrophages and activated T cells producing tumor necrosis factor alpha and gamma interferon, both required for the activation of the phagocytes. In 90% of immunocompetent humans, this response controls the infection. To understand why immunity fails in the other 10%, we studied the lungs of six patients who underwent surgery for incurable TB. Histologic examination of different lung lesions revealed heterogeneous morphology and distribution of acid-fast bacilli; only at the surface of cavities, i.e., in granulomas with a patent connection to the airways, were there numerous bacilli. The mutation profile of the isolates suggested that a single founder strain of Mycobacterium tuberculosis may undergo genetic changes during treatment, leading to acquisition of additional drug resistance independently in discrete physical locales. Additional drug resistance was preferentially observed at the cavity surface. Cytokine gene expression revealed that failure to control the bacilli was not associated with a generalized suppression of cellular immunity, since cytokine mRNA was up regulated in all lesions tested. Rather, a selective absence of CD4+ and CD8+ T cells was noted at the luminal surface of the cavity, preventing direct T-cell-macrophage interactions at this site, probably allowing luminal phagocytes to remain permissive for bacillary growth. In contrast, in the perinecrotic zone of the granulomas, the two cell types colocalized and bacillary numbers were substantially lower, suggesting that in this microenvironment an efficient bacteriostatic or bactericidal phagocyte population was generated.
机译：对肺结核（TB）的保护性免疫的特征是在肉芽肿的肺中形成肉芽肿，该肉芽肿由巨噬细胞和产生肿瘤坏死因子α和γ干扰素的活化T细胞组成，这都是吞噬细胞的激活所必需的。在90％具有免疫能力的人中，这种反应可控制感染。为了理解为什么免疫力在其他10％中会失败，我们研究了6名因不治之症接受手术治疗的患者的肺部。对不同肺部病变的组织学检查显示，形态和耐酸杆菌分布不均。仅在腔表面，即在与呼吸道有明显联系的肉芽肿中，才有大量杆菌。分离株的突变特征表明，结核分枝杆菌的单个创始菌株可能在治疗过程中发生遗传变化，从而导致在离散的物理场所独立获得额外的耐药性。优选在腔体表面观察到额外的耐药性。细胞因子基因的表达表明，控制细菌的失败与细胞免疫的普遍抑制无关，因为细胞因子mRNA在所有测试的病灶中均被上调。相反，在腔腔表面注意到选择性缺乏CD4 + 和CD8 + T细胞，可能阻止了该部位直接的T细胞-巨噬细胞相互作用。允许腔内吞噬细胞保持细菌生长。相反，在肉芽肿的坏死区，共定位的两种细胞类型和细菌数均较低，这表明在这种微环境中产生了有效的抑菌或杀菌吞噬细胞群。

著录项

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