对宿主血管源信号的拦截限制了真菌细菌的生长
Stefan H Oehlers1, Mark R Cronan1, Ninecia R Scott1
1Department of Molecular Genetics and Microbiology, Center for Microbial Pathogenesis, Duke University Medical Center, Durham, North Carolina 27710, USA.
Nature
|December 4, 2014
概括
结核颗粒瘤发展出血管,促进细菌的生长和传播. 抑制这种血管化,以及抗生素,可能为耐药结核病提供一种新的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 传染性疾病 传染性疾病
- 血管生物学 血管生物学
背景情况:
- 结核病 (TB) 的特征是颗粒瘤,复杂的细胞结构,形成响应致病性菌根菌.
- 这些颗粒瘤的发展和血管化对于疾病的进展和细菌的生存至关重要.
研究的目的:
- 研究血管新生 (新血管形成) 在结核颗粒瘤的发展中的作用.
- 探索抗血管性疗法作为结核病宿主导治疗的潜力.
主要方法:
- 利用了斑马鱼-Mycobacterium marinum感染模型,该模型模仿了人类结核病颗粒瘤.
- 采用静脉内显微镜实时可视化颗粒瘤血管化.
- 研究了对血管内皮生长因子 (VEGF) 途径的药理抑制的影响.
主要成果:
- 颗粒瘤的形成与血管生成密切相关,由局部缺氧和VEGFa诱导启动.
- 抑制VEGF信号减少了颗粒瘤血管化,减少了细菌负担,并限制了感染的传播.
- 抗血管原剂在与里芬素和美特罗尼达等抗生素结合使用时显示出协同效应.
结论:
- 菌根杆菌诱导细粒瘤血管化以促进它们的生长和传播.
- 向血管新生是一种有前途的宿主导结核病治疗策略,特别是耐药形式.
- 从癌症治疗中重新利用的抗血管原剂可能是结核病治疗方案的宝贵补充.
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