Alcohol resistance in Drosophila is modulated by the Toll innate immune pathway

Reduction in Toll pathway activity decreases ethanol resistance, while activation of the Toll pathway increases resistance. 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‐relate...

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Bibliographic Details
Published in:	Genes, brain and behavior Vol. 15; no. 4; pp. 382 - 394
Main Authors:	Troutwine, B. R., Ghezzi, A., Pietrzykowski, A. Z., Atkinson, N. S.
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-04-2016 John Wiley & Sons, Inc
Subjects:	Addiction Alcohol Alcohol Drinking - immunology alcohol resistance alcohol sensitivity alcoholism Animals Drosophila melanogaster Drosophila melanogaster - drug effects Drosophila melanogaster - genetics Drosophila melanogaster - immunology Drosophila Proteins - genetics Drosophila Proteins - immunology Drug Tolerance Ethanol Ethanol - pharmacology Female Immune system Immunity, Innate - physiology innate immunity Insects Models, Animal mutations neuroimmune NF‐κB Pneumoviridae RNAi Signal Transduction - drug effects tolerance Toll-Like Receptors - genetics Toll-Like Receptors - immunology NF-κB neuroimmune RNAi mutations Addiction alcoholism innate immunity alcohol sensitivity ethanol alcohol resistance tolerance
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Summary:	Reduction in Toll pathway activity decreases ethanol resistance, while activation of the Toll pathway increases resistance. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1601-1848 1601-183X
DOI:	10.1111/gbb.12288