Thus, at 10 days p.i., we can consider that the infected honeybees of our study displayed a level of N. ceranae invasion seen in forager honeybees. The first evidence of a synergistic interaction between Nosema RP6530 inhibitor infection and insecticide exposure in honeybees was described by Alaux et al.. These authors demonstrated that Nosema spp treatment combined with exposure to imidacloprid, another neonicotinoid, resulted in a higher JI-101 mortality of honeybees. Based on these results, we hypothesized that N. ceranae infection could alter the functioning of detoxification system. We assessed the ECOD and GST activities to test this hypothesis. In insects, ECOD and GST activities have often served as convenient measures of overall phases I and II metabolizing enzyme activities. In addition, levels of ECOD and GST activities have been associated with sensitivity to insecticides. Our results showed that ECOD activity remained unchanged at 10 days p.i, in fat body and midgut whereas GST activity increased significantly in both tissues. Therefore, these data indicated that the higher mortality observed after insecticide exposure in N. ceranae-infected honeybees was not strongly linked to a decrease in detoxification capacity. However, we cannot exclude that infection by N. ceranae could modify other enzymes involved in detoxification of these insecticides. Because this metabolic hypothesis failed to explain the sensitization process observed with mortality data, we assessed the effect of exposure to insecticides on spore production. Our results indicated that exposure to fipronil and thiacloprid had antagonist effects on spore production. Indeed, in comparison to infected honeybees not exposed to insecticides, the spore production decreased by about 33% during exposure to fipronil whereas the spore production increased by 40% with thiacloprid exposure. These results then, do not explain the mortality increase observed in the presence of insecticides. First, exposures to fipronil and thiacloprid induced an increase in mortality among infected honeybees but had opposite effects on spore production. Second, in the case of thiacloprid, the spore overproduction did not seem sufficient to explain the enhancement of honeybees�� mortality.