Activation of antibacterial autophagy by NADPH oxidases

Ju Huang, Veronica Canadien, Grace Y. Lam, Benjamin E. Steinberg, Mary C. Dinauer, Marco A.O. Magalhaes, Michael Glogauer, Sergio Grinstein, John H. Brumell

Research output: Contribution to journalArticle

370 Scopus citations

Abstract

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 Fcγ receptors (FcγRs) 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.

Original languageEnglish
Pages (from-to)6226-6231
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number15
DOIs
StatePublished - Apr 14 2009
Externally publishedYes

Keywords

  • Innate immunity
  • Phagosome
  • Reactive oxygen species
  • Salmonella
  • TLR

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    Huang, J., Canadien, V., Lam, G. Y., Steinberg, B. E., Dinauer, M. C., Magalhaes, M. A. O., Glogauer, M., Grinstein, S., & Brumell, J. H. (2009). Activation of antibacterial autophagy by NADPH oxidases. Proceedings of the National Academy of Sciences of the United States of America, 106(15), 6226-6231. https://doi.org/10.1073/pnas.0811045106