Nagging Questions Take Toll on Researchers: Differing Perspectives on Toll-like Receptors

Although the research featured in high-impact papers often resonates for years after the papers appear, these papers have actually remained at the center of debate, according to the authors and others in the field. The papers describe the toll-like receptor family of signaling proteins and their role in recognizing harmful bacterial cell wall components in mammals. Says Bruce Beutler, senior author on the first of these Hot Papers: "In the fullness of time, it has become obvious to all workers in the LPS field that TLR2 [toll-like receptor] does not transduce the LPS [bacterial lipopolysaccharide] signal, though such a role was unequivocally claimed by the Paul Godowski¹ and Mike Rothe² groups. In our 1998 Science paper, we emphatically stated that TLR2 could not be the LPS transducer. As we explained, the fact that a single mutation could totally abolish LPS signaling did not allow for two independent...