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TRAF3 protein is a key part of the early immune response to viruses

A protein called TRAF3, with a previously unknown job in immune cells, is actually a key part of a mechanism that triggers release of anti-virus molecules called type I interferons (IFNs) as part of the body's rapid response against these invaders, according to investigators that include a scientist continuing this work at St. Jude Children's Research Hospital.

The discovery of TRAF3's role helps to explain how immune cells called macrophages use sensing devices called Toll-like receptors (TLRs) to orchestrate just the right response to different types of infections. TLRs are on the outer membranes of macrophages and respond to germs by triggering the production of proteins called cytokines. Various cytokines regulate different biological functions that are important during immune responses, such as inflammation and protection against viruses. In addition, some cytokines contain anti-inflammatory activities, which curb potentially harmful inflammation.

The researchers showed that TRAF3 is not only essential for production of type I interferons, but also for production of IL-10, a protein that prevents inflammation. In fact, the team showed that cells lacking the gene for TRAF3 can't produce IL-10 and instead over-produce proteins that cause inflammation.

A report on these results appears online in the November 23 prepublication issue of Nature.

"The discovery that TRAF3 is also recruited to Toll-like receptors was important," says Hans Haecker, M.D., Ph.D., the first author of the paper and currently an assistant member of the St. Jude Department of Infectious Diseases. "It filled in an important piece of the puzzle of the front-line immune response to viruses that we didn't even realize was missing. Further research using this simple system will help solve the mystery of how macrophages can pick and choose among different strategies for combating specific infections." Haecker was at the Technical University of Munich and the Univ
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Contact: Carrie Strehlau
Carrie.Strehlau@stjude.org
901-495-2295
St. Jude Children's Research Hospital
13-Dec-2005


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