ASSOCIATION OF LEGIONELLA-PNEUMOPHILA WITH THE MACROPHAGE ENDOPLASMIC-RETICULUM

Legionella pneumophila replicates within a membrane-bounded compartmen t that is studded with ribosomes, In this study we investigated whethe r these ribosomes originate from the cytoplasmic pool or are associate d with host endoplasmic reticulum (ER), Immunofluorescence and electro n microscopic localization studies of ER proteins in macrophages infec ted with L. pneumophila indicated that the bacteria reside in a compar tment surrounded by ER, An L. pneumophila mutant that grows slowly in macrophages was slow to associate with host ER, providing genetic evid ence in support of the hypothesis that this specialized vacuole is req uired for intracellular bacterial growth, Ultrastructural studies, in which the ER luminal protein BiP was labeled by immunoperoxidase cytoc hemistry, revealed that L. pneumophila replication vacuoles resemble n ascent autophagosomes. Furthermore, short-term amino acid starvation o f macrophages, which stimulated host autophagy, increased association of the bacteria,vith the ER and enhanced bacterial growth. These resul ts are compatible with the hypothesis that L. pneumophila exploits the autophagy machinery of macrophages to establish an intracellular nich e favorable for replication.