Virus recognition by Toll-7 activates antiviral autophagy in Drosophila

Immunity. 2012 Apr 20;36(4):658-67. doi: 10.1016/j.immuni.2012.03.003. Epub 2012 Mar 29.

Abstract

Innate immunity is highly conserved and relies on pattern recognition receptors (PRRs) such as Toll-like receptors (identified through their homology to Drosophila Toll) for pathogen recognition. Although Drosophila Toll is vital for immune recognition and defense, roles for the other eight Drosophila Tolls in immunity have remained elusive. Here we have shown that Toll-7 is a PRR both in vitro and in adult flies; loss of Toll-7 led to increased vesicular stomatitis virus (VSV) replication and mortality. Toll-7, along with additional uncharacterized Drosophila Tolls, was transcriptionally induced by VSV infection. Furthermore, Toll-7 interacted with VSV at the plasma membrane and induced antiviral autophagy independently of the canonical Toll signaling pathway. These data uncover an evolutionarily conserved role for a second Drosophila Toll receptor that links viral recognition to autophagy and defense and suggest that other Drosophila Tolls may restrict specific as yet untested pathogens, perhaps via noncanonical signaling pathways.

Publication types

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

MeSH terms

  • Animals
  • Autophagy*
  • Cell Line
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Cricetinae
  • Drosophila melanogaster / immunology*
  • Drosophila melanogaster / virology
  • RNA Interference
  • RNA, Small Interfering
  • Signal Transduction
  • Toll-Like Receptor 7 / genetics
  • Toll-Like Receptor 7 / immunology*
  • Vesicular stomatitis Indiana virus / immunology*
  • Vesicular stomatitis Indiana virus / physiology
  • Vesicular stomatitis New Jersey virus / immunology*
  • Vesicular stomatitis New Jersey virus / physiology
  • Virus Replication

Substances

  • RNA, Small Interfering
  • Toll-Like Receptor 7