Morris Otto, Liu Xi, Domingues Celia, Runchel Christopher, Chai Andrea, Basith Shaherin, Tenev Tencho, Chen Haiyang, Choi Sangdun, Pennetta Giuseppa, Buchon Nicolas, Meier Pascal
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.
Department of Entomology, Cornell University, 5124 Comstock Hall, 129 Garden Avenue, Ithaca, NY 14853, USA.
Cell Host Microbe. 2016 Sep 14;20(3):283-295. doi: 10.1016/j.chom.2016.08.003.
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.
模式识别受体在感染后被激活，并触发对宿主防御至关重要的转录程序。严格调控NF-κB激活对于避免有害和失衡的反应至关重要。我们描述了Pickle，一种果蝇核IκB，它通过扭曲NF-κB二聚体库的转录输出，整合来自Imd和Toll途径的信号输入。Pickle与NF-κB蛋白Relish和组蛋白去乙酰化酶dHDAC1相互作用，选择性抑制Relish同型二聚体，而其他NF-κB二聚体组合则不受影响。Pickle选择性抑制Relish同型二聚体活性的能力有助于宿主获得适当的免疫力和机体健康。虽然缺失pickle会导致Relish靶基因的过度诱导，并在短期内提高宿主对病原菌的抵抗力，但pickle的长期失活会导致免疫耐受性丧失和寿命缩短。因此，Pickle允许产生平衡的免疫反应，既能保护宿主免受致病微生物的侵害，又能建立有益的共生宿主-微生物关系。
