Signal Integration by the IκB Protein Pickle Shapes Drosophila Innate Host Defense

Otto Morris, Xi Liu, Celia Domingues, Christopher Runchel, Andrea Chai, Shaherin Basith, Tencho Tenev, Haiyang Chen, Sangdun Choi, Giuseppa Pennetta, Nicolas Buchon, Pascal Meier

Research output: Contribution to journalArticlepeer-review

Abstract

Pattern recognition receptors are activated following infection and trigger transcriptional programs important for host defense. Tight regulation of NF-κB activation is critical to avoid detrimental and misbalanced responses. We describe Pickle, a Drosophila nuclear IκB that integrates signaling inputs from both the Imd and Toll pathways by skewing the transcriptional output of the NF-κB dimer repertoire. Pickle interacts with the NF-κB protein Relish and the histone deacetylase dHDAC1, selectively repressing Relish homodimers while leaving other NF-κB dimer combinations unscathed. Pickle's ability to selectively inhibit Relish homodimer activity contributes to proper host immunity and organismal health. Although loss of pickle results in hyper-induction of Relish target genes and improved host resistance to pathogenic bacteria in the short term, chronic inactivation of pickle causes loss of immune tolerance and shortened lifespan. Pickle therefore allows balanced immune responses that protect from pathogenic microbes while permitting the establishment of beneficial commensal host-microbe relationships.

Original languageEnglish
Pages (from-to)283-295
Number of pages13
JournalCell Host & Microbe
Volume20
Issue number3
DOIs
Publication statusPublished - 14 Sep 2016

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