Microbiota-dependent priming of antiviral intestinal immunity in Drosophila

Christine L. Sansone, Jonathan Cohen, Ari Yasunaga, Jie Xu, Greg Osborn, Harry Subramanian, Beth Gold, Nicolas Buchon, Sara Cherry

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Enteric pathogens must overcome intestinal defenses to establish infection. In Drosophila, the ERK signaling pathway inhibits enteric virus infection. The intestinal microflora also impacts immunity but its role in enteric viral infection is unknown. Here we show that two signals are required to activate antiviral ERK signaling in the intestinal epithelium. One signal depends on recognition of peptidoglycan from the microbiota, particularly from the commensal Acetobacter pomorum, which primes the NF-kB-dependent induction of a secreted factor, Pvf2. However, the microbiota is not sufficient to induce this pathway; a second virus-initiated signaling event involving release of transcriptional paused genes mediated by the kinase Cdk9 is also required for Pvf2 production. Pvf2 stimulates antiviral immunity by binding to the receptor tyrosine kinase PVR, which is necessary and sufficient for intestinal ERK responses. These findings demonstrate that sensing of specific commensals primes inflammatory signaling required for epithelial responses that restrict enteric viral infections.

Original languageEnglish (US)
Pages (from-to)571-581
Number of pages11
JournalCell Host and Microbe
Volume18
Issue number5
DOIs
StatePublished - Nov 11 2015

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Virology

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