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PMID: 15888080 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

Autophagy is an immediate macrophage response to Legionella pneumophila.

Cellular microbiology ·Vol. 7 ·No. 6 ·2005-06-00 ·Pages 765-78

Amer AO, Swanson MS

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.

MeSH Terms
Animals Autophagy/drug effects,physiology Endoplasmic Reticulum/metabolism,microbiology Escherichia coli/physiology In Vitro Techniques Legionella pneumophila/physiology Lysosomes/metabolism,microbiology Macrophages/metabolism,microbiology Mice Mice, Inbred C57BL Mutation Phagosomes/metabolism,microbiology Protein Transport Ubiquitin-Conjugating Enzymes/metabolism Vacuoles/metabolism,microbiology Virulence
Chemicals
Ubiquitin-Conjugating Enzymes
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Amer Amal O
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.
Swanson Michele S
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Article Info
Journal
Cellular microbiology
Abbr.
Cell Microbiol
ISSN
1462-5814
DOI
10.1111/j.1462-5822.2005.00509.x
Published
2005-06-00
Pages
765-78
Language
English
Region
England
NLM ID
100883691
PMCID
PMC1584279
Subset
IM
Grants
NIAID NIH HHS · R01 AI040694 · United States
NIAID NIH HHS · R01 AI040694-06AI · United States
External Links
PubMed source DOI: 10.1111/j.1462-5822.2005.00509.x PMC Full Text View journal details
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