Dynamic nature of host-pathogen interactions in Mycobacterium marinum granulomas
Dynamic nature of host-pathogen interactions in Mycobacterium marinum granulomas
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DOI：
10.1128/iai.69.12.7820-7831.2001
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发表时间：
2001-12-01
影响因子：
3.1
通讯作者：
Ramakrishnan, L
中科院分区：
文献类型：
--
作者：
Bouley, DM;Ghori, N;Ramakrishnan, L
海分枝杆菌引起免疫活性豹蛙（蛙）的长期亚临床肉芽肿感染。这些肉芽肿是由活化的巨噬细胞组成的有组织的集合体，与持续的人类结核感染有许多共同的形态学特征。我们研究了青蛙的器官与慢性铝。marinum感染使用透射电子显微镜结合免疫组织化学和酸性磷酸酶细胞化学，以更好地定义细菌-宿主的相互作用，在持续感染。细菌总是在巨噬细胞吞噬体内发现。这些吞噬体通常与溶酶体融合，与M. marinum。青蛙肉芽肿中受感染的巨噬细胞表现出不同程度的激活，如形态学变化所证明的，包括上皮样转化、最近的吞噬事件、吞噬溶酶体融合和细菌解体。我们的研究结果表明，即使是长期的肉芽肿是动态的环境中的宿主细胞活化和细菌营业额的水平，并建议不断复制的细菌和吞噬细胞杀伤，保持相对恒定的细菌数量之间的连续性，尽管建立了免疫反应。细胞内复制能力降低的突变菌株感染改变了平衡，导致细菌负荷大大降低，炎症灶与典型肉芽肿不同。
Mycobacterium marinum causes long-term subclinical granulomatous infection in immunocompetent leopard frogs (Rana pipiens). These granulomas, organized collections of activated macrophages, share many morphological features vith persistent human tuberculous infection. We examined organs of frogs with chronic Al. marinum infection using transmission electron microscopy in conjunction with immunohistochemistry and acid phosphatase cytochemistry to better define the bacterium-host interplay during persistent infection. Bacteria were always found within macrophage phagosomes. These phagosomes were often fused to lysosomes, in sharp contrast to those formed during in vitro infection of J774 macrophage-like cells by M. marinum. The infected macrophages in frog granulomas showed various levels of activation, as evidenced by morphological changes, including epithelioid transformation, recent phagocytic events, phagolysosomal fusion, and disintegration of bacteria. Our results demonstrate that even long-term granulomas are dynamic environments with regard to the level of host cell activation and bacterial turnover and suggest a continuum between constantly replicating bacteria and phagocytic killing that maintains relatively constant bacterial numbers despite an established immune response. Infection with a mutant bacterial strain with a reduced capacity for intracellular replication shifted the balance, leading to a greatly reduced bacterial burden and inflammatory foci that differed from typical granulomas.