MEMPHIS, Tenn., Dec. 13 /PRNewswire/ -- 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 have 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. Researchers already knew that a protein called TRAF6 is recruited to TLRs during the early phase of an immune response. But the current finding showed that TRAF3 is also recruited and plays a key role in determining the type of immune response generated by the macrophage.
A report on these results appears online in the November 23 prepublication issue of Nature.
“The discovery that TRAF3 is also recruited to TLRs is a big step toward solving the mystery of how macrophages can pick and choose among different strategies for combating specific infections,” says Hans Haecker, M.D., Ph.D., the first author of the paper and currently an assistant member of the Department of Infectious Diseases at St. Jude. Haecker was at the Technical University of Munich and the University of California, San Diego, when he worked on this project.
The results of the study suggest that the specific type of immune response triggered by TLR signaling depends on the relative amounts of TRAF3 and TRAF6 that are initially recruited and the different signaling proteins each of those proteins subsequently recruit to orchestrate the immune response. Other authors of the study include Vanessa Redecke, Li-Chung Hsu, Gang G. Wang, Mark P. Kamps, Eyal Raz and Michael Karin (University of California, San Diego); Blagoy Blagoev, Irina Kratchmarova and Matthias Mann (University of Southern Denmark); Hermann Wagner and Georg Haecker (Technische Universitat Munchen, Munich, Germany).
This work was supported in part by the National Institutes of Health, the American Cancer Society and the Deutsche Forschungsgemeinschaft.
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