QnAs with Bruce Beutler

Abstract

Most people can tell when their bodies are in the throes of an infection, but Bruce Beutler is on a mission to determine where and how this recognition actually begins, at the level of microbe-sensing immune cell molecules. A professor of immunology at the University of Texas Southwestern and a recently elected member of the National Academy of Sciences, Beutler shared the 2011 Nobel Prize in Physiology or Medicine for demonstrating an infection-sensing role for the mammalian immune cell-surface receptor, TLR4. This protein activates the innate immune response—the body’s primary line of defense against pathogens—upon detecting LPS, a structural component of certain bacteria. Beutler, who has long used genetic methods to tease apart the molecular details of the immune system, discusses his findings with PNAS. Bruce Beutler. > PNAS:Your Nobel Prize-winning work began decades ago when you isolated from mice a factor known as tumor necrosis factor (TNF), which is made by immune cells called macrophages. How did that discovery lead to your research on TLR4? > Beutler:It was just quite by chance that I went to a laboratory as a postdoctoral fellow where a factor hypothetically associated with wasting in chronic disease was being isolated. I isolated that factor, which I found to be identical to TNF. I found that …