title: Signal Integration by the IκB Protein Pickle Shapes Drosophila Innate Host Defense.
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.
authors.affiliation: The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research, Mary-Jean Mitchell Green Building, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK. Electronic address: otto.morris@icr.ac.uk.
authors.forename: Otto
authors.initials: O
authors.lastname: Morris
authors.affiliation: Department of Entomology, Cornell University, 5124 Comstock Hall, 129 Garden Avenue, Ithaca, NY 14853, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.affiliation: The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research, Mary-Jean Mitchell Green Building, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK.
authors.forename: Celia
authors.initials: C
authors.lastname: Domingues
authors.affiliation: The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research, Mary-Jean Mitchell Green Building, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Runchel
authors.affiliation: Euan MacDonald Centre for Motor Neuron Disease Research, Centre for Integrative Physiology, The University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Chai
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea; National Leading Research Laboratory of Molecular Modeling & Drug Design, College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Korea.
authors.forename: Shaherin
authors.initials: S
authors.lastname: Basith
authors.affiliation: The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research, Mary-Jean Mitchell Green Building, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK.
authors.forename: Tencho
authors.initials: T
authors.lastname: Tenev
authors.affiliation: School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea.
authors.forename: Sangdun
authors.initials: S
authors.lastname: Choi
authors.affiliation: Euan MacDonald Centre for Motor Neuron Disease Research, Centre for Integrative Physiology, The University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Pennetta
authors.affiliation: Department of Entomology, Cornell University, 5124 Comstock Hall, 129 Garden Avenue, Ithaca, NY 14853, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Buchon
authors.affiliation: The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research, Mary-Jean Mitchell Green Building, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK. Electronic address: pmeier@icr.ac.uk.
authors.forename: Pascal
authors.initials: P
authors.lastname: Meier
mesh_terms: D000818:Animals; D004330:Drosophila / Q000276:immunology / Q000502:physiology*; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D056284:Histone Deacetylase 1 / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism*; D007113:Immunity, Innate; D011485:Protein Binding; D025941:Protein Interaction Mapping; D015398:Signal Transduction; D014157:Transcription Factors / Q000037:antagonists & inhibitors*
chemical_list: D029721:Drosophila Proteins; D020672:I-kappa B Proteins; C101626:Rel protein, Drosophila; D014157:Transcription Factors; C512966:HDAC1 protein, Drosophila; D056284:Histone Deacetylase 1
keywords: Drosophila; Imd; IκB; NF-κB; innate immunity