Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis

Miguel A. Sanjuan, et al. 2007. Nature 450, 1253-1257

Speaker: Jeng-Liang Tsai (蔡政良)                       Time: 13:00~14:00, Mar. 19, 2008

Commentator: Dr. Chiou-Feng Lin (林秋烽 博士)               Place: Room 601

Abstract:

Autophagy and phagocytosis are discrete but related processes that are important for cellular defense from pathogens. Phagocytosis entails the engulfment and internalization of extracellular organisms¹, whereas autophagy involves the formation of a double-membrane barrier around proteins, pathogens or organelles already present in the cytosol². The phagosome or autophagosome then fuses with lysosomes and its contents are destroyed. In this study, the authors showed that when macrophages phagocytosed special beads carrying pieces of germs, there was a rapid movement of the autophagy-associated LC3 proteins to the developing phagosome. The scientists then fed particles called zymosan (killed yeast cells) to macrophages that lacked TLR2. In those macrophages, the movement of LC3 to phagosomes in response to zymosan ingestion was significantly slowed. This suggested that TLR was required for triggering movement of LC3 to the phagosome. The team also showed that two proteins critical for autophagy, ATG5 and ATG7, were key to the ability of macrophages to enable phagosomes to mature. For example, macrophages lacking ATG5 were not able to fuse phagosomes with lysosomes. While macrophages lacking ATG7 were able to phagocytize live yeast cells, the yeast were more likely to survive degradation in macrophages without ATG7 than yeast ingested by normal macrophages. This strongly suggested that TLR recruits parts of the autophagy machinery to enable the phagosome to fully develop and fuse with the lysosome even if autophagy itself doesn't occur simultaneously.

References:

1.         Desjardins, M., Houde, M. & Gagnon, E. Phagocytosis: the convoluted way from nutrition to adaptive immunity. Immunol Rev 207, 158-65 (2005).

2.         Levine, B. & Deretic, V. Unveiling the roles of autophagy in innate and adaptive immunity. Nat Rev Immunol 7, 767-77 (2007).