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Role of Drosophila IKKγ in a Toll-independent antibacterial immune response

Abstract

We have generated, by ethylmethane sulfonate mutagenesis, loss-of-function mutants in the Drosophila homolog of the mammalian I-κB kinase (IKK) complex component IKKγ (also called NEMO). Our data show that Drosophila IKKγ is required for the Relish-dependent immune induction of the genes encoding antibacterial peptides and for resistance to infections by Escherichia coli. However, it is not required for the Toll-DIF–dependent antifungal host defense. The results indicate distinct control mechanisms of the Rel-like transactivators DIF and Relish in the Drosophila innate immune response and show that Drosophila Toll does not signal through a IKKγ-dependent signaling complex. Thus, in contrast to the vertebrate inflammatory response, IKKγ is required for the activation of only one immune signaling pathway in Drosophila.

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Figure 1: Immune-inducibility of most antimicrobial peptide genes is affected in kenny mutants.
Figure 2: key mutant flies are highly sensitive to bacterial, but not natural fungal, infections.
Figure 3: key is required for Diptericin promoter binding of Relish but not for DIF nuclear uptake.
Figure 4: The Drosophila NEMO-IKKγ homolog is mutated in key flies.
Figure 5: The one Rel protein–one transduction pathway model in Drosophila.

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Acknowledgements

We thank D. Hultmark for Relish fly stocks; E. Langley and M.-C. Criqui for the DIF antibody; M.-C. Criqui for participating in initial phases of the screen; C. Troccon, S. Storck and S. Dissel for help with the screen; P. Georgel for help with gel retardation assays; R. Lanot for phagocytosis assays; and J.-M. Reichhart and T. Maniatis for their interest and support. Supported by CNRS, the Human Frontiers in Science Program (to J. H.), the Helen Hey Whitney Foundation (to N. S.), NIH grants (GM29379, GM59919 to T. Maniatis; 1PO1 AI44220-02 to A. Ezekowitz and J. H.), the French Ministère de l'Education Nationale, de la Recherche et de la Technologie (PRFMMIP) and the Fondation pour la Recherche Médicale (aide à l'implantation de nouvelles équipes to D. F).

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Correspondence to Dominique Ferrandon.

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Rutschmann, S., Jung, A., Zhou, R. et al. Role of Drosophila IKKγ in a Toll-independent antibacterial immune response. Nat Immunol 1, 342–347 (2000). https://doi.org/10.1038/79801

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