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St. Jude Children's Research Hospital investigators have discovered that immune system cells that engulf and destroy germs in the body enlist help for this task from a common housekeeping mechanism that most cells use to keep their interiors healthy, a finding that is likely to help researchers understand how the body defends itself against infections and how cancer cells can resist chemotherapy drugs before they have a chance to work.
The discovery of this link between the two mechanisms --- phagocytosis (engulfing germs) and autophagy (housekeeping) --- suggests that a common mechanism that triggers both processes individually also links them together using a common set of signals. The processes of phagocytosis and autophagy enclose various cellular structures or germs within a sac that fuses with a bag of digestive enzymes called the lysosome. The lysosome then releases the digestive enzymes into the sac and the enzymes degrade its contents. A report on the discovery appears in the Dec. 20 issue of the journal "Nature."
The St. Jude team discovered that TLR, a protein on the surface of cells that phagocytize germs, is the link between this "outside job" of germ engulfment and the housekeeping "inside jobs" done by autophagy, such as destroying germs that have forced their way into the cell and breaking down defective molecules to obtain nutrients during times of stress. Specifically, TLR recruits special proteins that orchestrate autophagy and uses them to supervise phagocytosis and the formation of the digestive sac called the phagosome.
"Our findings strongly suggest 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," said Douglas Green, Ph.D., chair of the St. Jude Department of Immunology and senior author of the report.
"Now that we discovered that phagocytosis uses some of the same biochemical signals as autophagy does, we can use that information to solve the mystery of how autophagy works," said Miguel Sanjuan, Ph.D., a staff scientist in Green's laboratory and first author of the report.