title: 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.
authors.affiliation: Dipartimento di Agraria, Laboratorio di Entomologia E. Tremblay, Università degli Studi di Napoli Federico II, I-80055 Portici, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Di Prisco
authors.forename: Valeria
authors.initials: V
authors.lastname: Cavaliere
authors.forename: Desiderato
authors.initials: D
authors.lastname: Annoscia
authors.forename: Paola
authors.initials: P
authors.lastname: Varricchio
authors.forename: Emilio
authors.initials: E
authors.lastname: Caprio
authors.forename: Francesco
authors.initials: F
authors.lastname: Nazzi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gargiulo
authors.forename: Francesco
authors.initials: F
authors.lastname: Pennacchio
mesh_terms: D000691:Anabasine / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000032:analysis; D001516:Bees / Q000187:drug effects / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D055785:Gene Knockdown Techniques; D006146:Guanidines / Q000737:chemistry / Q000633:toxicity*; D007113:Immunity, Innate / Q000187:drug effects*; D007306:Insecticides / Q000737:chemistry / Q000633:toxicity*; D007558:Italy; D000073943:Neonicotinoids; D060888:Real-Time Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013844:Thiazoles / Q000737:chemistry / Q000633:toxicity*
chemical_list: D023181:Antimicrobial Cationic Peptides; D006146:Guanidines; D007306:Insecticides; D000073943:Neonicotinoids; D013844:Thiazoles; C061361:apidaecin; C480342:clothianidin; D000691:Anabasine
keywords: Apis mellifera; DWV; NLR (CLR); neuroimmunity; toxicology