title: Autophagy is an immediate macrophage response to Legionella pneumophila.
abstract: After ingestion by macrophages, Legionella pneumophila enter spacious vacuoles that are quickly enveloped by endoplasmic reticulum (ER), then slowly transferred to lysosomes. Here we demonstrate that the macrophage autophagy machinery recognizes the pathogen phagosome as cargo for lysosome delivery. The autophagy conjugation enzyme Atg7 immediately translocated to phagosomes harbouring virulent Legionella. Subsequently, Atg8, a second autophagy enzyme, and monodansyl-cadaverine (MDC), a dye that accumulates in acidic autophagosomes, decorated the pathogen vacuoles. The autophagy machinery responded to 10-30 kDa species released into culture supernatants by Type IV secretion-competent Legionella, as judged by the macrophages' processing of Atg8 and formation of vacuoles that sequentially acquired Atg7, Atg8 and MDC. When compared with autophagosomes stimulated by rapamycin, Legionella vacuoles acquired Atg7, Atg8 and MDC more slowly, and Atg8 processing was also delayed. Moreover, compared with autophagosomes of Legionella-permissive naip5 mutant A/J macrophages, those of resistant C57BL/6 J macrophages matured quickly, preventing efficient Legionella replication. Accordingly, we discuss a model in which macrophages elevate autophagy as a barrier to infection, a decision influenced by regulatory interactions between Naip proteins and caspases.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, 6734 Medical Science Building II, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0620, USA.
authors.forename: Amal O
authors.initials: AO
authors.lastname: Amer
authors.forename: Michele S
authors.initials: MS
authors.lastname: Swanson
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000382:microbiology; D004926:Escherichia coli / Q000502:physiology; D066298:In Vitro Techniques; D016952:Legionella pneumophila / Q000502:physiology*; D008247:Lysosomes / Q000378:metabolism / Q000382:microbiology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D010588:Phagosomes / Q000378:metabolism / Q000382:microbiology; D021381:Protein Transport; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism / Q000382:microbiology; D014774:Virulence
chemical_list: D044763:Ubiquitin-Conjugating Enzymes