Autophagy induced by 2-deoxy-D-glucose suppresses intracellular  multiplication of Legionella pneumophila in A/J mouse macrophages.
Legionella pneumophila Philadelphia-1 (Lp-1) can grow intracellularly in A/J mouse peritoneal macrophages (A/J Mphi). We previously reported that 2-deoxy-D-glucose (2dG), when added in macrophage culture medium, inhibited the intracellular multiplication of Lp-1 in A/J Mphi. We found that 1 mM of 2dG causes LC3-II-conversion that reflects an induction of autophagy and that 1 and 10 mM of 2dG induced apoptosis associated with caspase-4 activation. We therefore investigated whether 2dG-induced autophagy or apoptosis suppresses the replication ofLp-1 in 2dG-treated A/J Mphi. When the autophagy-related (Atg)gene Atg5 was knocked down by RNA interference, the Atg5-siRNA-transfected cells revealed an enhanced replication of Lp-1 in A/J Mphi compared with the non-targetting siRNA-transfected cells. However, caspase-4 inhibitor did not affect the 2dG-induced inhibition of intracellular multiplication of Lp-1 in A/J Mphi. These findings suggested that autophagy, not apoptosis, suppressed the intracellular growth of Lp-1 in A/J Mphi when 1 or 10 mM of 2dG were added to the culture media.
Matsuda
Fumiko
F
Department of Bacteriology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan. fmatsuda@bact.med.kyushu-u.ac.jp
Fujii
Jun
J
Yoshida
Shin-ichi
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001343:Autophagy / Q000187:drug effects*; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D053471:Caspases, Initiator; D003847:Deoxyglucose / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015151:Immunoblotting; D042541:Intracellular Space / Q000187:drug effects* / Q000382:microbiology*; D016952:Legionella pneumophila / Q000187:drug effects / Q000254:growth & development* / Q000648:ultrastructure; D017737:Macrophages, Peritoneal / Q000166:cytology* / Q000201:enzymology / Q000382:microbiology* / Q000648:ultrastructure; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010588:Phagosomes / Q000187:drug effects / Q000648:ultrastructure; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D015854:Up-Regulation / Q000187:drug effects
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D003847:Deoxyglucose; C101136:Casp4 protein, mouse; D020169:Caspases; D053471:Caspases, Initiator