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Microplastic (MPs) pollution has emerged as a global ecological concern, however, the impact of MPs exposure, particularly in conjunction with other pollutants such as glyphosate (GLY) on honey bee remains unknown. This study investigated the effects of exposure to different concentrations of MPs and their combination with GLY on honey bee larvae development, or during the larvae period, regulation of major detoxification, antioxidant and immune genes, and oxidative stress biomarkers. Results revealed that combined exposure to MPs and GLY decreased larvae survivorship and weight, while exposure to MPs alone showed no significant differences. Both MPs and GLY alone downregulated the defensin-1 gene, but only combined exposure with GLY downregulated the hymenoptaecin gene and increased catalase enzyme activity. The data suggest a synergistic effect of MPs and GLY, leading to immunosuppression and reduced larvae survival and weight. These findings highlight potential risks of two prevalent environmental pollutants on honey bee health., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Giulia Angelica Mitton reports financial support was provided by National Agency for Promotion of Science and Technology. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)