St. Jude finds link between cellular defense processes, showing how cancer cel...( St. Jude Children's Research Hospita...),Health

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 mechanismsphagocytosis (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.

Autophagy is a cell-survival jack-of-all-trades, and were trying to understand the signals that trigger its onset, said Douglas Green, Ph.D., chair of the St. Jude Department of Immunology and the papers senior author. This process developed so early in the evolution of life that at least some types of microorganisms must have learned how to avoid this defensive response of the cell to being invaded. We want to know how invading microorganisms avoid being destroyed by autophagy and learn how cancer cells use autophagy to resist chemotherapy drugs before they have a chance to work.

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. Specifically, TLR recruits special proteins that orchestrate autophagy and uses them to supervise phagocytosis and the formation of the digestive
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