Caffeine helps limit viral infections in honey bees
This study evaluated the influence of caffeine on the honey bee immune system.
Gene expression levels were measured to investigate the interaction between caffeine and deformed wing virus (DWV). The effect of caffeine on honey bee immunity is largely unknown. In humans, high caffeine concentrations can mitigate damage caused by inflammation by inhibiting phosphodiesterase (PDE) activity, increasing intracellular cAMP and activating the PKA pathway. This may explain the changes in gene expression observed in this study, since the PKA pathway also helps regulate immunity.
Analysis of immune gene expression showed significant increases after caffeine treatment in DWV-infected bees: parseph and myd88 in the Toll pathway; PGRPLC, tak1, kenny and tab in the Imd pathway; and lysozyme-1 (Lys-1), prophenoloxidase-activating enzyme (PPOact) and amPPO. Both Toll and Imd pathways have previously been implicated in antiviral defence in insects. Our results also showed that caffeine treatment before DWV infection could inhibit infection. This suggests that caffeine may strengthen immunity by increasing expression of genes in pathways known to influence immune responses, such as Toll and Imd, and help protect bees against viral infections.
Following DWV infection, immune-related gene expression was upregulated. Although previous studies indicated that DWV can suppress host immunity, those findings concerned prolonged, latent infection involving Varroa destructor and DWV. In our experiment, the virus was given to healthy bees, so the situation differed. This acute infection triggered a peak in the bees’ immune response to viral invasion. The effect of caffeine on gene expression in 16-day-old bees had not previously been explored.
Caffeine is a natural compound found in the nectar of some plants, so bees can readily ingest it from their environment. Overall, caffeine has the potential to improve resistance to viral infection. In 16-day-old bees, its effect was similar but less extensive and positive than at other ages. Caffeine inhibits DWV replication by improving carbohydrate metabolism.
To investigate further how caffeine stimulates immune-response gene expression, DWV replication was analysed in infected bees receiving a diet with or without caffeine. DWV genome copy numbers were significantly lower in bees receiving caffeine, suggesting that increased immune-response gene expression suppressed viral replication. An optimal immune response requires considerable energy; we therefore hypothesised that caffeine stimulates these genes through positive effects on carbohydrate metabolism pathways. To test this, real-time PCR was used to analyse genes involved in glycolysis and the tricarboxylic acid (TCA) cycle in bees fed with or without caffeine. Although differences were not statistically significant, expression of genes in glycolysis and the TCA cycle showed an upward trend.
Caffeine also inhibited infection by other common honey bee viruses. Infected bees received caffeine in their diet to assess its effects on viral activity in the host. Quantification of viral gene expression by real-time PCR showed a significant decrease in six viral targets in caffeine-treated bees, except for black queen cell virus (BQCV) and Varroa destructor virus (VDV).
Yun-Heng Lu et al.
Adapted from Identification of Immune Regulatory Genes in Apis mellifera through Caffeine Treatment — Insects 2020, 11, 516; doi: 10.3390/insects11080516
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