Listeriolysin O allows Listeria monocytogenes replication in macrophage vacuoles
Listeriolysin O allows Listeria monocytogenes replication in macrophage vacuoles
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DOI：
10.1038/nature06479
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发表时间：
2008-01-17
期刊：
影响因子：
64.8
通讯作者：
Brumell, John H.
中科院分区：
文献类型：
--
作者：
Birmingham, Cheryl L.;Canadien, Veronica;Brumell, John H.
单核细胞增生李斯特菌是一种细胞内细菌病原体，在急性感染期间在宿主细胞的胞质溶胶中快速复制（1）。令人惊讶的是，在严重联合免疫缺陷（SCID）小鼠的持续感染期间，发现这些细菌占据肝肉芽肿巨噬细胞中的空泡（2）。这里我们证明L.单核细胞增多症可以在巨噬细胞内的空泡中复制。在感染21天的SCID小鼠的肝脏中，我们观察到大的LAMP1（+）隔室中的细菌，我们称之为宽敞的含李斯特菌的吞噬体（SLAPs）。还在体外观察到SLAP，并且发现其是以自噬依赖性方式产生的非酸性和非降解隔室。发现SLAPs中细菌的复制率与胞质溶胶中的细菌的复制率相比降低。李斯特菌溶血素O（LLO，由hly编码）是李斯特菌所必需的一种成孔毒素.单核细胞增多症毒力（1），是必要的和足够的SHBE形成。A L.低LLO表达的单核细胞增多症突变体的吞噬体逃逸受损，但在72小时内在SLAPs中复制缓慢。因此，我们的研究揭示了LLO在促进L。单核细胞增多症复制的空泡，并提出了一种机制，这种病原体可以建立持续感染宿主巨噬细胞。
Listeria monocytogenes is an intracellular bacterial pathogen that replicates rapidly in the cytosol of host cells during acute infection(1). Surprisingly, these bacteria were found to occupy vacuoles in liver granuloma macrophages during persistent infection of severe combined immunodeficient ( SCID) mice(2). Here we show that L. monocytogenes can replicate in vacuoles within macrophages. In livers of SCID mice infected for 21 days, we observed bacteria in large LAMP1(+) compartments that we termed spacious Listeria- containing phagosomes ( SLAPs). SLAPs were also observed in vitro, and were found to be non- acidic and non-degradative compartments that are generated in an autophagy-dependent manner. The replication rate of bacteria in SLAPs was found to be reduced compared to the rate of those in the cytosol. Listeriolysin O ( LLO, encoded by hly), a pore- forming toxin essential for L. monocytogenes virulence(1), was necessary and sufficient for SLAP formation. A L. monocytogenes mutant with low LLO expression was impaired for phagosome escape but replicated slowly in SLAPs over a 72 h period. Therefore, our studies reveal a role for LLO in promoting L. monocytogenes replication in vacuoles and suggest a mechanism by which this pathogen can establish persistent infection in host macrophages.