Genome-wide RNAi screen identifies genes involved in intestinal pathogenic bacterial infection

Science. 2009 Jul 17;325(5938):340-3. doi: 10.1126/science.1173164. Epub 2009 Jun 11.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Proliferation
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / immunology
  • Drosophila melanogaster / microbiology*
  • Epithelial Cells / cytology
  • Epithelial Cells / physiology
  • Genome, Insect*
  • Hemocytes / immunology
  • Hemocytes / metabolism
  • Hemocytes / microbiology
  • Homeostasis
  • Immunity, Innate / genetics*
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Janus Kinases / genetics
  • Janus Kinases / metabolism
  • Models, Animal
  • RNA Interference*
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / metabolism
  • Serratia Infections / genetics
  • Serratia Infections / immunology*
  • Serratia Infections / microbiology
  • Serratia marcescens / immunology*
  • Serratia marcescens / physiology
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / physiology

Substances

  • Drosophila Proteins
  • STAT Transcription Factors
  • Janus Kinases