Neonicotinoid clothianidin adversely affects insect immunity and promotes replication of a viral pathogen in honey bees

Abstract

Large-scale losses of honey bee colonies represent a poorly understood problem of global importance. Both biotic and abiotic factors are involved in this phenomenon that is often associated with high loads of parasites and pathogens. A stronger impact of pathogens in honey bees exposed to neonicotinoid insecticides has been reported, but the causal link between insecticide exposure and the possible immune alteration of honey bees remains elusive. Here, we demonstrate that the neonicotinoid insecticide clothianidin negatively modulates NF-κB immune signaling in insects and adversely affects honey bee antiviral defenses controlled by this transcription factor. We have identified in insects a negative modulator of NF-κB activation, which is a leucine-rich repeat protein. Exposure to clothianidin, by enhancing the transcription of the gene encoding this inhibitor, reduces immune defenses and promotes the replication of the deformed wing virus in honey bees bearing covert infections. This honey bee immunosuppression is similarly induced by a different neonicotinoid, imidacloprid, but not by the organophosphate chlorpyriphos, which does not affect NF-κB signaling. The occurrence at sublethal doses of this insecticide-induced viral proliferation suggests that the studied neonicotinoids might have a negative effect at the field level. Our experiments uncover a further level of regulation of the immune response in insects and set the stage for studies on neural modulation of immunity in animals. Furthermore, this study has implications for the conservation of bees, as it will contribute to the definition of more appropriate guidelines for testing chronic or sublethal effects of pesticides used in agriculture.Apis mellifera | DWV | NLR (CLR) | neuroimmunity | toxicology

Transcriptional signatures of parasitization and markers of colony decline in Varroa-infested honey bees (Apis mellifera)

“…In honey bees, it has been shown that some neonicotinoid insecticides, agonists of nicotinic acetylcholine receptors, have the potential of disrupting the delicate balance of host-virus interactions orchestrated by NF-kB, resulting in viral amplification (Di Prisco et al, 2013).…”

“…According to Nazzi et al (2012), dorsal plays a critical role in antiviral defence in bees such that its down-regulation is linked to increased DWV replication. The role of this gene in antiviral defence has been supported by a study showing that a treatment with the neonicotinoid insecticide clothianidin, that indirectly targets the same gene, results in high levels of DWV replication (Di Prisco et al, 2013). Interestingly, the role of dorsal in antiviral defence does not seem to be restricted to honey bees, since it has been shown that the Toll-Dorsal Pathway is required for resistance to viral oral infection in the fruit fly as well (Ferreira et al, 2014).…”

A sting in the spit: widespread cross‐infection of multiple RNA viruses across wild and managed bees

“…Recent studies have reported interactions between sublethal doses of neonicotinoid pesticides and pathogens, with significant impacts on virus replication and host immunity (Di Prisco et al . 2013) and bee mortality (Doublet et al . 2014).…”

Honeybee health in Africa—a review

“…Pesticides, in particular, can have a negative and harmful impact on the behaviour and physiology of honeybees that can directly influence the overall health of the colony (Yang et al 2008;Di Prisco et al 2013;Williamson and Wright 2013;Smith et al 2013). These negative effects can become even more pronounced when honeybees are simultaneously exposed to multiple stressors, i.e.…”