title: Microbiota-Dependent Priming of Antiviral Intestinal Immunity in Drosophila.
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.
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Sansone
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cohen
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Ari
authors.initials: A
authors.lastname: Yasunaga
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Osborn
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Harry
authors.initials: H
authors.lastname: Subramanian
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Gold
authors.affiliation: Department of Entomology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Buchon
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. Electronic address: cherrys@mail.med.upenn.edu.
authors.forename: Sara
authors.initials: S
authors.lastname: Cherry
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification / Q000378:metabolism; D042863:Cyclin-Dependent Kinase 9 / Q000378:metabolism; D004330:Drosophila / Q000033:anatomy & histology / Q000276:immunology* / Q000382:microbiology / Q000821:virology*; D029721:Drosophila Proteins / Q000378:metabolism; D007113:Immunity, Innate; D020935:MAP Kinase Signaling System; D064307:Microbiota; D010457:Peptidoglycan / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D010457:Peptidoglycan; C438368:Pvr protein, Drosophila; D020794:Receptor Protein-Tyrosine Kinases; D042863:Cyclin-Dependent Kinase 9