{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:51:05Z","timestamp":1790970665574,"version":"4.1.0"},"reference-count":188,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research at Imam Mohammad Ibn Saud Islamic University","award":["IMSIU-DDRSP2601"],"award-info":[{"award-number":["IMSIU-DDRSP2601"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Insects"],"abstract":"<jats:p>Honeybee (Apis mellifera) health is governed by the integrated action of detoxification, immunity, and microbiota within complex environmental contexts. The coordinated detoxification system (DETOXome), primarily active in the midgut, fat body, and Malpighian tubules, includes cytochrome P450s, glutathione S transferases, carboxylesterases, and ABC transporters, and functions in concert with innate immune pathways such as Toll, Imd, Jak\/STAT, JNK, antimicrobial peptides, and RNA interference. Cellular maintenance mechanisms, including heat shock proteins, proteostasis, and antioxidant defenses, support these systems under chemical, thermal, and pathogen-induced stress. Multi-stressor exposures encompassing pesticides, pathogens, nutritional limitations, and climate variations interact to affect physiological resilience, behavior, and colony function. This review synthesizes molecular, organ-specific, and colony-level evidence to provide a mechanistic framework connecting environmental stressors to detoxification and immune responses. Predictive markers derived from transcriptomic, proteomic, and microbiome analyses offer early detection of sublethal stress, while genomic and selective breeding strategies hold the potential to enhance honeybee resilience. By integrating stress pathways across biological scales, this review advances a unified model of honeybee health that moves beyond descriptive lists to highlight cross-system interactions driving colony survival.<\/jats:p>","DOI":"10.3390\/insects17060559","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:37:26Z","timestamp":1780454246000},"page":"559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic and Molecular Mechanisms of Detoxification and Immunity in Honeybees (Apis mellifera)"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6561-0996","authenticated-orcid":false,"given":"Zunair","family":"Ahsan","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, 88 South University Rd, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8633-9387","authenticated-orcid":false,"given":"Faouzi","family":"Haouala","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Sciences, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usama","family":"Abdullah","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, 88 South University Rd, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umar Sajid","family":"Kayani","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, 88 South University Rd, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1574-4216","authenticated-orcid":false,"given":"Mokhtar","family":"Rejili","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Sciences, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105410","DOI":"10.1016\/j.pestbp.2023.105410","article-title":"Expression profile of the entire detoxification gene inventory of the western honeybee, Apis mellifera across life stages","volume":"192","author":"Maiwald","year":"2023","journal-title":"Pestic. 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