This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Genetic and Molecular Mechanisms of Detoxification and Immunity in Honeybees (Apis mellifera)
1
College of Animal Science and Technology, Yangzhou University, 88 South University Rd, Yangzhou 225009, China
2
Department of Life Biology, College of Sciences, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia
*
Author to whom correspondence should be addressed.
Insects 2026, 17(6), 559; https://doi.org/10.3390/insects17060559 (registering DOI)
Submission received: 21 April 2026
/
Revised: 25 May 2026
/
Accepted: 26 May 2026
/
Published: 28 May 2026
(This article belongs to the Special Issue Bees: Physiology, Immunity and Developmental Biology)
Simple Summary
The fat body, midgut, and Malpighian tubules coordinate the integration of gut microbiota, innate immunity, and detoxification pathways in honeybee health. Rather than functioning independently, these molecular systems are interconnected and supported by behavioral defenses at the colony level, forming a multi-layered response to environmental stressors. However, the combined pressures of infections, pesticide exposure, and nutritional limitations can gradually compromise this resilience. Even sublethal disruptions at the molecular level may lead to behavioral changes and reductions in colony performance. These findings highlight the importance of considering coordinated physiological and ecological mechanisms in understanding honeybee health under contemporary environmental challenges.
Abstract
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.
