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在双重感染的小鼠巨噬细胞中构建庇护鸟分枝杆菌和贝氏柯克斯体(II期)的嵌合吞噬体:一项超微结构研究。

Construction of chimeric phagosomes that shelter Mycobacterium avium and Coxiella burnetii (phase II) in doubly infected mouse macrophages: an ultrastructural study.

作者信息

de Chastellier C, Thibon M, Rabinovitch M

机构信息

INSERM U411, UFR de Médecine Necker, Paris, France.

出版信息

Eur J Cell Biol. 1999 Aug;78(8):580-92. doi: 10.1016/S0171-9335(99)80024-7.

Abstract

Dual infection of cells may divert pathogens to intracellular compartments different from those occupied in mono-infected cells. In the present studies, mouse bone marrow in vitro-derived macrophages were first infected with virulent Mycobacterium avium, which are normally singly lodged within tight phagosomes. These phagosomes do not mature; they undergo homotypic fusion with early endosomes and do not fuse with lysosomes. Seven days later, the cultures were superinfected with phase II (non-virulent) Coxiella burnetii, organisms sheltered in lysosome- (or prelysosome)-like, multi-occupancy phagosomes. The latter can attain large size and engage in efficient homo- and heterotypic fusion with other phagosomes. Cultures were fixed for transmission electron microscopy 6, 12, 24, and 48 h later. Other M. avium-infected cultures were superinfected with amastigotes of the trypanosomatid flagellate Leishmania amazonensis, which are also sheltered in lysosome- (or prelysosome)-like multi-occupancy vacuoles, and fixed at the same time periods. Chimeric phagosomes containing both M. avium and C. burnetii, were found already at 6 h and the proportion of M. avium that colocalized with C. burnetii in the same phagosomes reached over 90% after 48 h. In such phagosomes, both organisms were ultrastructurally well preserved. In contrast, colocalization of M. avium and L. amazonensis was rarely found. Speculative scenarios that could underlie the formation of chimeric phagosomes could involve delayed maturation of C. burnetii-containing phagosomes in presence of M. avium, which would allow for fusion of C. burnetii- and M. avium-containing phagosomes; the production, by C. burnetii, of molecules that upregulate the fusion of M. avium-containing phagosomes with those that contain C. burnetii; and the secretion of factors that could favour the survival of M. avium within chimeric vacuoles.

摘要

细胞的双重感染可能会使病原体转移到与单感染细胞中所占据的不同的细胞内区室。在本研究中,首先用强毒鸟分枝杆菌感染体外培养的小鼠骨髓巨噬细胞,这些细菌通常单个存在于紧密的吞噬体中。这些吞噬体不会成熟;它们与早期内体进行同型融合,并且不与溶酶体融合。七天后,培养物再感染II期(无毒)伯纳特立克次体,这些生物体存在于类似溶酶体(或前溶酶体)的多菌占据的吞噬体中。后者可以变得很大,并与其他吞噬体进行有效的同型和异型融合。在6、12、24和48小时后对培养物进行固定以进行透射电子显微镜观察。其他感染鸟分枝杆菌的培养物再感染锥虫鞭毛虫亚马逊利什曼原虫的无鞭毛体,它们也存在于类似溶酶体(或前溶酶体)的多菌占据的液泡中,并在相同时间段进行固定。在6小时时就已经发现了同时含有鸟分枝杆菌和伯纳特立克次体的嵌合吞噬体,48小时后,在同一吞噬体中与伯纳特立克次体共定位的鸟分枝杆菌比例达到90%以上。在这样的吞噬体中,两种生物体在超微结构上都保存完好。相比之下,很少发现鸟分枝杆菌和亚马逊利什曼原虫的共定位。嵌合吞噬体形成的潜在推测情况可能包括在存在鸟分枝杆菌的情况下,含伯纳特立克次体的吞噬体成熟延迟,这将允许含伯纳特立克次体和含鸟分枝杆菌的吞噬体融合;伯纳特立克次体产生上调含鸟分枝杆菌的吞噬体与含伯纳特立克次体的吞噬体融合的分子;以及分泌有利于鸟分枝杆菌在嵌合液泡内存活的因子。

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