RRC ID 35157
Author Sansone CL, Cohen J, Yasunaga A, Xu J, Osborn G, Subramanian H, Gold B, Buchon N, Cherry S.
Title Microbiota-Dependent Priming of Antiviral Intestinal Immunity in Drosophila.
Journal Cell Host Microbe
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.
Volume 18(5)
Pages 571-81
Published 2015-11-11
DOI 10.1016/j.chom.2015.10.010
PII S1931-3128(15)00420-5
PMID 26567510
PMC PMC4648705
MeSH Animals Bacteria / classification Bacteria / metabolism Cyclin-Dependent Kinase 9 / metabolism Drosophila / anatomy & histology Drosophila / immunology* Drosophila / microbiology Drosophila / virology* Drosophila Proteins / metabolism Immunity, Innate* MAP Kinase Signaling System Microbiota* Peptidoglycan / metabolism Receptor Protein-Tyrosine Kinases / metabolism
IF 15.923
Times Cited 58
Drosophila 8222R-2 8222R-3