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首页> 外文期刊>Infection and immunity >Mycobacterium marinum Infection of Adult Zebrafish Causes Caseating Granulomatous Tuberculosis and Is Moderated by Adaptive Immunity
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Mycobacterium marinum Infection of Adult Zebrafish Causes Caseating Granulomatous Tuberculosis and Is Moderated by Adaptive Immunity

机译：成年斑马鱼的海洋分枝杆菌感染引起干酪肉芽肿性结核病，并由适应性免疫调节

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The zebrafish, a genetically tractable model vertebrate, is naturally susceptible to tuberculosis caused by Mycobacterium marinum, a close genetic relative of the causative agent of human tuberculosis, Mycobacterium tuberculosis. We previously developed a zebrafish embryo-M. marinum infection model to study host-pathogen interactions in the context of innate immunity. Here, we have constructed a flowthrough fish facility for the large-scale longitudinal study of M. marinum-induced tuberculosis in adult zebrafish where both innate and adaptive immunity are operant. We find that zebrafish are exquisitely susceptible to M. marinum strain M. Intraperitoneal injection of five organisms produces persistent granulomatous tuberculosis, while the injection of ～9,000 organisms leads to acute, fulminant disease. Bacterial burden, extent of disease, pathology, and host mortality progress in a time- and dose-dependent fashion. Zebrafish tuberculous granulomas undergo caseous necrosis, similar to human tuberculous granulomas. In contrast to mammalian tuberculous granulomas, zebrafish lesions contain few lymphocytes, calling into question the role of adaptive immunity in fish tuberculosis. However, like rag1 mutant mice infected with M. tuberculosis, we find that rag1 mutant zebrafish are hypersusceptible to M. marinum infection, demonstrating that the control of fish tuberculosis is dependent on adaptive immunity. We confirm the previous finding that M. marinum ΔRD1 mutants are attenuated in adult zebrafish and extend this finding to show that ΔRD1 predominantly produces nonnecrotizing, loose macrophage aggregates. This observation suggests that the macrophage aggregation defect associated with ΔRD1 attenuation in zebrafish embryos is ongoing during adult infection.
机译：斑马鱼是具有遗传易感性的模型脊椎动物，自然易受“结核分枝杆菌”引起的结核病的侵害，“结核分枝杆菌”是人类结核病致病菌“结核分枝杆菌”的近亲。我们之前开发了斑马鱼胚胎- M。 marinum 感染模型研究先天免疫背景下的宿主-病原体相互作用。在这里，我们为 M的大型纵向研究建立了流水式鱼类设施。斑马鱼在成年斑马鱼中由海马氏菌引起的结核病，先天免疫和适应性免疫均起作用。我们发现斑马鱼对 M非常敏感。 marinum 菌株M.腹腔内注射5种生物会产生持续性肉芽肿性结核，而注射9,000种生物则会导致急性暴发性疾病。细菌负担，疾病程度，病理学和宿主死亡率以时间和剂量依赖性方式发展。斑马鱼结核性肉芽肿经历干酪样坏死，类似于人结核性肉芽肿。与哺乳动物的结核性肉芽肿相比，斑马鱼的病变中几乎没有淋巴细胞，这使适应性免疫在鱼结核中的作用受到质疑。但是，像感染了 M的 rag1 突变小鼠一样。结核，我们发现 rag1 突变斑马鱼对 M易感。感染，表明对鱼结核的控制取决于适应性免疫。我们确认先前的发现是 M。斑马鱼中的Marinum ΔRD1突变体减毒并扩展了这一发现，从而表明ΔRD1主要产生非坏死性，松散的巨噬细胞聚集体。该观察结果表明，在成年感染期间，斑马鱼胚胎中与ΔRD1衰减相关的巨噬细胞聚集缺陷仍在继续。

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