Toll-8/Tollo negatively regulates antimicrobial response in the Drosophila respiratory epithelium

PLoS Pathog. 2011 Oct;7(10):e1002319. doi: 10.1371/journal.ppat.1002319. Epub 2011 Oct 13.

Abstract

Barrier epithelia that are persistently exposed to microbes have evolved potent immune tools to eliminate such pathogens. If mechanisms that control Drosophila systemic responses are well-characterized, the epithelial immune responses remain poorly understood. Here, we performed a genetic dissection of the cascades activated during the immune response of the Drosophila airway epithelium i.e. trachea. We present evidence that bacteria induced-antimicrobial peptide (AMP) production in the trachea is controlled by two signalling cascades. AMP gene transcription is activated by the inducible IMD pathway that acts non-cell autonomously in trachea. This IMD-dependent AMP activation is antagonized by a constitutively active signalling module involving the receptor Toll-8/Tollo, the ligand Spätzle2/DNT1 and Ect-4, the Drosophila ortholog of the human Sterile alpha and HEAT/ARMadillo motif (SARM). Our data show that, in addition to Toll-1 whose function is essential during the systemic immune response, Drosophila relies on another Toll family member to control the immune response in the respiratory epithelium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / biosynthesis
  • Armadillo Domain Proteins / genetics
  • Armadillo Domain Proteins / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / immunology
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / immunology*
  • Drosophila melanogaster / microbiology
  • Immunity, Innate
  • Insect Hormones / metabolism*
  • Mutation
  • RNA Interference
  • RNA, Small Interfering
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / microbiology
  • Signal Transduction
  • Toll-Like Receptor 8 / genetics
  • Toll-Like Receptor 8 / metabolism*
  • Trachea / immunology
  • Trachea / microbiology

Substances

  • Antimicrobial Cationic Peptides
  • Armadillo Domain Proteins
  • Drosophila Proteins
  • Insect Hormones
  • RNA, Small Interfering
  • Toll-Like Receptor 8
  • ect protein, Drosophila
  • imd protein, Drosophila
  • spz protein, Drosophila