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Science 325 (5938): 340-343

Copyright © 2009 by the American Association for the Advancement of Science

Genome-Wide RNAi Screen Identifies Genes Involved in Intestinal Pathogenic Bacterial Infection

Shane J. F. Cronin,1,* Nadine T. Nehme,2,* Stefanie Limmer,2 Samuel Liegeois,2 J. Andrew Pospisilik,1 Daniel Schramek,1 Andreas Leibbrandt,1 Ricardo de Matos Simoes,3 Susanne Gruber,1 Urszula Puc,1 Ingo Ebersberger,3 Tamara Zoranovic,1 G. Gregory Neely,1 Arndt von Haeseler,3 Dominique Ferrandon,2,{dagger},{ddagger} Josef M. Penninger1,{dagger}

Abstract: Innate immunity represents the first line of defense in animals. We report a genome-wide in vivo Drosophila RNA interference screen to uncover genes involved in susceptibility or resistance to intestinal infection with the bacterium Serratia marcescens. We first employed whole-organism gene suppression, followed by tissue-specific silencing in gut epithelium or hemocytes to identify several hundred genes involved in intestinal antibacterial immunity. Among the pathways identified, we showed that the JAK-STAT signaling pathway controls host defense in the gut by regulating stem cell proliferation and thus epithelial cell homeostasis. Therefore, we revealed multiple genes involved in antibacterial defense and the regulation of innate immunity.

1 IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria.
2 Equipe Fondation Recherche Médicale, UPR 9022 du CNRS, Institut de Biologie Moléculaire et Cellulaire du CNRS, F-67084 Strasbourg, France.
3 Center for Integrative Bioinformatics (CIBIV), University of Vienna, Medical University of Vienna, University of Veterinary Medicine, A-1030 Vienna, Austria.

* These authors contributed equally to this work.

{dagger} This work is based on equal contributions from the laboratories of the last two authors.

{ddagger} To whom correspondence should be addressed. E-mail: d.ferrandon{at}ibmc.u-strasbg.fr

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