Legionella pneumophila Replication Vacuoles Mature into Acidic, Endocytic Organelles

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摘要：

After ingestion by macrophages,Legionella pneumophilainhibits acidification and maturation of its phagosome. After a 6–10-h lag period, the bacteria replicate for 10–14 h until macrophage lysis releases dozens of progeny. To examine whether the growth phase of intracellularL.pneumophiladetermines the fate of its phagosome, interactions between the endosomal network and pathogen vacuoles were analyzed throughout the primary infection period. Surprisingly, asL.pneumophilareplicated exponentially, a significant proportion of the vacuoles acquired lysosomal characteristics. By 18 h, 70% contained lysosomal-associated membrane protein 1 (LAMP-1) and 40% contained cathepsin D; 50% of the vacuoles could be labeled by endocytosis, and the pH of this population of vacuoles averaged 5.6. Moreover,L.pneumophilaappeared to survive and replicate within lysosomal compartments: vacuoles harboring more than five bacteria also contained LAMP-1, inhibition of vacuole acidification and maturation by bafilomycin A1 inhibited bacterial replication, bacteria within endosomal vacuoles responded to a metabolic inducer by expressing agfpreporter gene, and replicating bacteria obtained from macrophages, but not broth, were acid resistant. Understanding howL.pneumophilafirst evades and then exploits the endosomal pathway to replicate within macrophages may reveal the mechanisms governing phagosome maturation, a process also manipulated byMycobacteria,Leishmania, andCoxiella.

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关键词：

pathogenesis autophagy phagosomes lysosomes macrophages

DOI：

10.1084/jem.192.9.1261

被引量：

491

年份：

2000