{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:27:17Z","timestamp":1785414437335,"version":"3.56.0"},"reference-count":26,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2023-NR076655"],"award-info":[{"award-number":["RS-2023-NR076655"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"award":["RS-2023-NR076655"],"award-info":[{"award-number":["RS-2023-NR076655"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Insects"],"abstract":"<jats:p>Ethanol is a pervasive chemical stressor in fermentative environments and represents a major ecological challenge for Drosophila melanogaster, a species that naturally inhabits decaying fruits. Although ethanol tolerance has traditionally been attributed to detoxification and antioxidant pathways, accumulating evidence indicates that immune-related genes, particularly those encoding immune deficiency (IMD) pathway-associated antimicrobial peptides (IMD-AMPs), contribute importantly to chemical stress adaptation. Previous studies have demonstrated that IMD-AMP induction is required for ethanol tolerance; however, whether elevated IMD-AMP expression alone is sufficient to enhance tolerance has remained unresolved. In this study, we investigated the functional significance of IMD-AMP upregulation in ethanol tolerance using dietary propolis as an experimental immune-modulating agent. D. melanogaster were reared throughout their life cycle on propolis-supplemented diets and subsequently exposed to ethanol. Propolis-fed flies exhibited significantly enhanced survival under ethanol stress compared with control flies. Notably, this increased tolerance was not accompanied by upregulation of classical ethanol metabolism genes or broad induction of antioxidant-related genes. Instead, propolis feeding increased baseline and early-stage expression of IMD-AMP genes, including Diptericin A (DptA), Diptericin B (DptB), Attacin (AttC), and Metchnikowin (Mtk) before and during ethanol exposure. These findings suggest IMD-AMP upregulation is positively associated with enhanced ethanol tolerance in D. melanogaster. Our results establish a proactive role for immune-related pathways in chemical stress resistance and extend the functional scope of AMPs beyond pathogen defense. This study identifies IMD-AMPs as key effectors linking immune activation to physiological adaptation under ethanol-induced chemical stress.<\/jats:p>","DOI":"10.3390\/insects17060542","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T13:12:08Z","timestamp":1779455528000},"page":"542","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pre-Emptive Upregulation of Antimicrobial Peptides by Dietary Propolis Improves Ethanol Tolerance in Drosophila melanogaster"],"prefix":"10.3390","volume":"17","author":[{"given":"JooHeon","family":"Cha","sequence":"first","affiliation":[{"name":"Department of Vector Entomology, Kyungpook National University, Sangju 37224, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0003-6604","authenticated-orcid":false,"given":"Young Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Vector Entomology, Kyungpook National University, Sangju 37224, Republic of Korea"},{"name":"Research Institute of Invertebrate Vector, Kyungpook National University, Sangju 37224, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","first-page":"245","article-title":"Overview: How is alcohol metabolized by the body?","volume":"29","author":"Zakhari","year":"2006","journal-title":"Alcohol Res. Health"},{"key":"ref_2","first-page":"287","article-title":"First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid","volume":"54","author":"Ighodaro","year":"2018","journal-title":"Alex. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1023\/A:1022931816351","article-title":"Identification of odors from overripe mango that attract vinegar flies, Drosophila melanogaster","volume":"29","author":"Zhu","year":"2003","journal-title":"J. Chem. Ecol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4137","DOI":"10.1021\/acsomega.0c04025","article-title":"A new model of alcoholic fermentation under a byproduct inhibitory effect","volume":"6","author":"Zentou","year":"2021","journal-title":"ACS Omega"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1534\/g3.114.015040","article-title":"Developmental ethanol exposure leads to dysregulation of lipid metabolism and oxidative stress in Drosophila","volume":"5","author":"Bortolazzo","year":"2015","journal-title":"G3"},{"key":"ref_6","first-page":"719","article-title":"Ethanol behavioral responses in Drosophila","volume":"2023","author":"Catalano","year":"2023","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1111\/1748-5967.12326","article-title":"Comparative analyses of susceptibility to chemicals associated with fermentation between Drosophila melanogaster and Drosophila suzukii","volume":"48","author":"Kim","year":"2018","journal-title":"Entomol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"104552","DOI":"10.1016\/j.pestbp.2020.02.018","article-title":"Identification of transcriptional responsive genes to acetic acid, ethanol, and 2-phenylethanol exposure in Drosophila melanogaster","volume":"165","author":"Seong","year":"2020","journal-title":"Pestic. Biochem. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"105210","DOI":"10.1016\/j.pestbp.2022.105210","article-title":"Expression of antimicrobial peptides associated with different susceptibilities to environmental chemicals in Drosophila suzukii and Drosophila melanogaster","volume":"187","author":"Kim","year":"2022","journal-title":"Pestic. Biochem. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.coi.2019.11.008","article-title":"New insights on Drosophila antimicrobial peptide function in host defense and beyond","volume":"62","author":"Hanson","year":"2020","journal-title":"Curr. Opin. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1051\/apido\/2010016","article-title":"Propolis and bee health: The natural history and significance of resin use by honey bees","volume":"41","author":"Spivak","year":"2010","journal-title":"Apidologie"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/hdy.1991.4","article-title":"On the developmental theory of ageing. I. Starvation resistance and longevity in Drosophila melanogaster in relation to pre-adult breeding conditions","volume":"66","author":"Zwaan","year":"1991","journal-title":"Heredity"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1002\/ps.2280","article-title":"Laboratory survival of Drosophila suzukii under simulated winter conditions of the Pacific Northwest and seasonal field trapping in five primary regions of small and stone fruit production in the United States","volume":"67","author":"Dalton","year":"2011","journal-title":"Pest Manag. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.aspen.2020.01.008","article-title":"Evaluation of reference genes for gene expression studies using quantitative real-time PCR in Drosophila melanogaster after chemical exposures","volume":"23","author":"Kim","year":"2020","journal-title":"J. Asia-Pac. Entomol."},{"key":"ref_15","unstructured":"Chandler, J.A., Innocent, L.V., Yang, J.L., Eisen, M.B., and Ludington, W.B. (2017). Microbiome-by-ethanol interactions impact Drosophila melanogaster fitness and physiology. bioRxiv, 217240."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kim, H., Kim, Y., Roh, G.H., and Kim, Y.H. (2023). Comparison of preference for chemicals associated with fruit fermentation between Drosophila melanogaster and Drosophila suzukii and between virgin and mated D. melanogaster. Insects, 14.","DOI":"10.3390\/insects14040382"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1093\/jee\/tow019","article-title":"The biochemical adaptations of spotted wing Drosophila (Diptera: Drosophilidae) to fresh fruits reduced fructose concentrations and glutathione-s transferase activities","volume":"109","author":"Nguyen","year":"2016","journal-title":"J. Econ. Entomol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s12263-009-0159-9","article-title":"Ethanol-induced oxidative stress: Basic knowledge","volume":"5","author":"Comporti","year":"2010","journal-title":"Genes Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.lfs.2007.05.005","article-title":"Alcohol-induced oxidative stress","volume":"81","author":"Das","year":"2007","journal-title":"Life Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1543809","DOI":"10.1155\/2016\/1543809","article-title":"Lipids and oxidative stress associated with ethanol-induced neurological damage","volume":"2016","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Cho, K.H., and Kang, S.O. (2025). The Gut Microbiota of Drosophila melanogaster: A Model for Host\u2013Microbe Interactions in Metabolism, Immunity, Behavior, and Disease. Microorganisms, 13.","DOI":"10.3390\/microorganisms13112515"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.dci.2017.11.008","article-title":"Beyond immunity: The Imd pathway as a coordinator of host defense, organismal physiology and behavior","volume":"83","author":"Zhai","year":"2018","journal-title":"Dev. Comp. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.dci.2013.05.014","article-title":"The Drosophila IMD pathway in the activation of the humoral immune response","volume":"42","author":"Kleino","year":"2014","journal-title":"Dev. Comp. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1146\/annurev.immunol.25.022106.141615","article-title":"The host defense of Drosophila melanogaster","volume":"25","author":"Lemaitre","year":"2007","journal-title":"Annu. Rev. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3390\/molecules19010078","article-title":"Structure and antioxidant activity of polyphenols derived from propolis","volume":"19","author":"Stojko","year":"2013","journal-title":"Molecules"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s13592-017-0553-z","article-title":"Propolis consumption ramps up the immune response in honey bees infected with bacteria","volume":"49","author":"Turcatto","year":"2018","journal-title":"Apidologie"}],"container-title":["Insects"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4450\/17\/6\/542\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:14:59Z","timestamp":1780546499000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4450\/17\/6\/542"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":26,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["insects17060542"],"URL":"https:\/\/doi.org\/10.3390\/insects17060542","relation":{},"ISSN":["2075-4450"],"issn-type":[{"value":"2075-4450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,22]]}}}