A reverse genetic analysis of components
of the Toll signaling pathway in Caenorhabditis elegans
Nathalie Pujol (1,13), Elizabeth M. Link (3,7,13) , Leo X. Liu (3,8,13) ,C. Léopold Kurz (2) , Geneviève Alloing (4,5,9), Man-Wah Tan (4,5,10), Keith P. Ray (6), Roberto Solari (6,11), Carl D. Johnson (3,12), and Jonathan J. Ewbank (2).
Background: Both animals and plants respond rapidly to pathogens by inducing the expression of defense-related genes. Whether such an inducible system of innate immunity is present in the model nematode Caenorhabditis elegans is currently an open question. Among conserved signaling pathways important for innate immunity, the Toll pathway is the best characterized. In Drosophila, this pathway also has an essential developmental rôle. C. elegans possesses structural homologs of components of this pathway, and this observation raises the possibility that a Toll pathway might also function in nematodes to trigger defense mechanisms or to control development.
Results: We have generated and characterized deletion mutants for four genes supposed to function in a nematode Toll signaling pathway. These genes are tol-1, trf-1, pik-1, and ikb-1 and are homologous to the Drosophila melanogaster Toll, dTraf, pelle, and cactus genes, respectively. Of these four genes, only tol-1 is required for nematode development. None of them are important for the resistance of C. elegans to a number of pathogens. On the other hand, C. elegans is capable of distinguishing different bacterial species and has a tendency to avoid certain pathogens, including Serratia marcescens. The tol-1 mutants are defective in their avoidance of pathogenic S. marcescens, although other chemosensory behaviors are wild type.
Conclusions: In C. elegans, tol-1 is important for development and pathogen recognition, as is Toll in Drosophila, but remarkably for the latter rôle, it functions in the context of a behavioral mechanism that keeps worms away from potential danger.
Addresses: (1) Laboratoire de Génétique
et Physiologie du Développement and (2) Centre d'Immunologie
de Marseille-Luminy, Institut National de la Santé et de
la Recherche Médicale/Centre National pour la Recherche
Scientifique/Université de la Mediterranée, Marseille
13288, France. (3) NemaPharm, Inc., Cambridge, Massachusetts 02139,
USA. (4) Department of Genetics, Harvard Medical School, Boston,
Massachusetts 02114, USA. (5) Department of Molecular Biology,
Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
(6) Glaxo Wellcome Research, Stevenage SG12NY, United Kingdom.
Present addresses: (7) Division of Genetic
Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
37232, USA. (8) Cambria Biosciences, Bedford, Massachusetts 01730,
USA. (9) Laboratoire de Biologie Veégétale et Microbiologie,
Université de Nice-Sophia Antipolis, Nice 06108, France.
(10) Department of Genetics, Stanford University School of
Medicine, Stanford, California 94305, USA. (11) Abingworth Management
Ltd, London SW1Y6DN, United Kingdom. (12) NemaPharm Group, Axys
Pharmaceuticals, South San Francisco 94080, USA.
Correspondence: Jonathan J. Ewbank
E-mail: ewbank@ciml.univ-mrs.fr
(13) These authors contributed equally to this work.