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The road to Toll

Nature Reviews Immunology volume 4, pages 521–527 (2004)Cite this article

Abstract

A few years ago, it would have been difficult to argue that elucidating the mechanisms of disease resistance in the fruit fly, Drosophila melanogaster, would provide new insights into mammalian immunity. Yet the finding that the Drosophila protein Toll mediates immune responses to fungal infection had a pioneering role in the identification of Toll-like receptors as essential regulators of mammalian host defence, and it fundamentally altered our understanding of innate immunity. In this Landmark article, I describe the thought processes and the experimental steps that defined Toll as a key regulator of Drosophila immune responses.

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Figure 1: Structure of the Toll and IL-1 receptors.
Figure 2: Toll mutants are highly susceptible to fungal infection.
Figure 3: The Toll and Imd pathways.

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Acknowledgements

I thank Jules Hoffmann and all of my former colleagues for the stimulating and encouraging environment in Strasbourg, France, and Nicolas Vodovar for providing the original illustration of figure 3. I am also indebted to the generous spirit of the Drosophila-research community, including Kathy Matthews at the Bloomington Stock Center, Bloomington, United States, and Iris Koch and Dirk Beuchle at the Tübingen Stock Centre, Tübingen, Germany, for providing the many fly stocks that made this work possible. My laboratory is supported by the Centre National de la Recherche Scientifique, France, and the Schlumberger and Bettencourt Foundations, France.

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  1. the Centre de Génétique Moléculaire, Centre National de la Recherche Scientifique, Gif-sur-Yvette, F-91198, France

    Bruno Lemaitre

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DATABASES

Entrez Gene

CD14

IκB

IL-1R

MD2

TLR4

FlyBase

Bc

Cactus

Cecropin A1

Dif

Diptericin

Dorsal

Drosomycin

Easter

Gastrulation defective

imd

Myd88

Pelle

Relish

Serpin-27A

snail

Snake

Spätzle

Toll-9

Tube

twist

FURTHER INFORMATION

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Lemaitre, B. The road to Toll. Nat Rev Immunol 4, 521–527 (2004). https://doi.org/10.1038/nri1390

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