Taking Toll of Toll-Like Receptors

Courtesy of Alan Aderem BAR-CODED BACTERIA: Combined activation of Toll-Like Receptors (TLRs) produces different specific responses. In this example, Microbe 1 activates TLRs 4 and 5, and is therefore likely to be a Gram-negative, flagellated bacterium. Microbe 2 activates TLR 5 and TLR 2/6, and is therefore likely to be Gram-positive and flagellated. Because of slightly different specificities, Microbe 3 would elicit a different response. Twas a head-scratcher: Twelve years ago, resear

Karen Young Kreeger

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Twas a head-scratcher: Twelve years ago, researchers found that a receptor, known for its role in a fruit fly dorsoventral patterning called Toll, was related to an important mammalian immune receptor called interleukin-1 (IL-1), a pro-inflammatory cytokine.¹ "How could this be?" recalls biochemistry professor Luke O'Neill, Trinity College, Dublin. "We have IL-1, which is inflammatory, and Toll, which is developmental.... Why would they be so similar?" But then it was shown in the adult fly that Toll has a role in antifungal defense.²

Since 1996, numerous researchers have investigated Toll-like receptors (TLRs) in mammals, which are involved in innate immunity, the body's first response to infection. Innate immunity is inborn; acquired immunity, which involves such downstream immune system components as dendritic cells and antigens, is obtained through lifelong contact with pathogens.

Four papers in 2001 added more pieces to the ever-evolving, complex TLR story.3-6 These researchers began detailing a clearer ...

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