TY - JOUR
T1 - Microbiota-dependent priming of antiviral intestinal immunity in Drosophila
AU - Sansone, Christine L.
AU - Cohen, Jonathan
AU - Yasunaga, Ari
AU - Xu, Jie
AU - Osborn, Greg
AU - Subramanian, Harry
AU - Gold, Beth
AU - Buchon, Nicolas
AU - Cherry, Sara
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/11/11
Y1 - 2015/11/11
N2 - 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.
AB - 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.
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U2 - 10.1016/j.chom.2015.10.010
DO - 10.1016/j.chom.2015.10.010
M3 - Article
C2 - 26567510
AN - SCOPUS:84947426731
SN - 1931-3128
VL - 18
SP - 571
EP - 581
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 5
ER -