PMID- 19339495
OWN - NLM
STAT- MEDLINE
DCOM- 20090512
LR  - 20230815
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 106
IP  - 15
DP  - 2009 Apr 14
TI  - Activation of antibacterial autophagy by NADPH oxidases.
PG  - 6226-31
LID - 10.1073/pnas.0811045106 [doi]
AB  - Autophagy plays an important role in immunity to microbial pathogens. The 
      autophagy system can target bacteria in phagosomes, promoting phagosome 
      maturation and preventing pathogen escape into the cytosol. Recently, Toll-like 
      receptor (TLR) signaling from phagosomes was found to initiate their targeting by 
      the autophagy system, but the mechanism by which TLR signaling activates 
      autophagy is unclear. Here we show that autophagy targeting of phagosomes is not 
      exclusive to those containing TLR ligands. Engagement of either TLRs or the 
      Fcgamma receptors (FcgammaRs) during phagocytosis induced recruitment of the 
      autophagy protein LC3 to phagosomes with similar kinetics. Both receptors are 
      known to activate the NOX2 NADPH oxidase, which plays a central role in microbial 
      killing by phagocytes through the generation of reactive oxygen species (ROS). We 
      found that NOX2-generated ROS are necessary for LC3 recruitment to phagosomes. 
      Antibacterial autophagy in human epithelial cells, which do not express NOX2, was 
      also dependent on ROS generation. These data reveal a coupling of oxidative and 
      nonoxidative killing activities of the NOX2 NADPH oxidase in phagocytes through 
      autophagy. Furthermore, our results suggest a general role for members of the NOX 
      family in regulating autophagy.
FAU - Huang, Ju
AU  - Huang J
AD  - Cell Biology Program, Hospital for Sick Children, Toronto, ON, Canada M5G 1X8.
FAU - Canadien, Veronica
AU  - Canadien V
FAU - Lam, Grace Y
AU  - Lam GY
FAU - Steinberg, Benjamin E
AU  - Steinberg BE
FAU - Dinauer, Mary C
AU  - Dinauer MC
FAU - Magalhaes, Marco A O
AU  - Magalhaes MA
FAU - Glogauer, Michael
AU  - Glogauer M
FAU - Grinstein, Sergio
AU  - Grinstein S
FAU - Brumell, John H
AU  - Brumell JH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090401
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Receptors, IgG)
RN  - EC 1.6.3.- (NADPH Oxidases)
SB  - IM
MH  - Animals
MH  - Autophagy/*immunology
MH  - Cell Line
MH  - Epithelial Cells/cytology/enzymology/*immunology/*microbiology
MH  - Humans
MH  - Mice
MH  - NADPH Oxidases/genetics/*metabolism
MH  - Phagosomes/immunology
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, Antigen, T-Cell/immunology
MH  - Receptors, IgG/immunology
MH  - Salmonella typhimurium/*immunology
MH  - Signal Transduction/immunology
PMC - PMC2664152
COIS- The authors declare no conflict of interest.
EDAT- 2009/04/03 09:00
MHDA- 2009/05/13 09:00
PMCR- 2009/04/01
CRDT- 2009/04/03 09:00
PHST- 2009/04/03 09:00 [entrez]
PHST- 2009/04/03 09:00 [pubmed]
PHST- 2009/05/13 09:00 [medline]
PHST- 2009/04/01 00:00 [pmc-release]
AID - 0811045106 [pii]
AID - 7416 [pii]
AID - 10.1073/pnas.0811045106 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6226-31. doi: 
      10.1073/pnas.0811045106. Epub 2009 Apr 1.