title: Alcohol resistance in Drosophila is modulated by the Toll innate immune pathway.
abstract: A growing body of evidence has shown that alcohol alters the activity of the innate immune system and that changes in innate immune system activity can influence alcohol-related behaviors. Here, we show that the Toll innate immune signaling pathway modulates the level of alcohol resistance in Drosophila. In humans, a low level of response to alcohol is correlated with increased risk of developing an alcohol use disorder. The Toll signaling pathway was originally discovered in, and has been extensively studied in Drosophila. The Toll pathway is a major regulator of innate immunity in Drosophila, and mammalian Toll-like receptor signaling has been implicated in alcohol responses. Here, we use Drosophila-specific genetic tools to test eight genes in the Toll signaling pathway for effects on the level of response to ethanol. We show that increasing the activity of the pathway increases ethanol resistance whereas decreasing the pathway activity reduces ethanol resistance. Furthermore, we show that gene products known to be outputs of innate immune signaling are rapidly induced following ethanol exposure. The interaction between the Toll signaling pathway and ethanol is rooted in the natural history of Drosophila melanogaster.
authors.affiliation: Department of Neuroscience, The Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX.
authors.forename: B R
authors.initials: BR
authors.lastname: Troutwine
authors.affiliation: Department of Neuroscience, The Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX.
authors.forename: A
authors.initials: A
authors.lastname: Ghezzi
authors.affiliation: The Biologically Inspired Neural & Dynamical Systems (BINDS) Lab, Department of Computer Science, University of Massachusetts Amherst, Amherst, MA, USA.
authors.forename: A Z
authors.initials: AZ
authors.lastname: Pietrzykowski
authors.affiliation: Department of Neuroscience, The Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX.
authors.forename: N S
authors.initials: NS
authors.lastname: Atkinson
mesh_terms: D000428:Alcohol Drinking / Q000276:immunology; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000276:immunology; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D007113:Immunity, Innate / Q000502:physiology; D023421:Models, Animal; D015398:Signal Transduction / Q000187:drug effects; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology*
chemical_list: D029721:Drosophila Proteins; D051193:Toll-Like Receptors; D000431:Ethanol
keywords: Addiction; NF-κB; RNAi; alcohol resistance; alcohol sensitivity; alcoholism; ethanol; innate immunity; mutations; neuroimmune; tolerance