title: Ingested human insulin inhibits the mosquito NF-κB-dependent immune response to Plasmodium falciparum.
abstract: We showed previously that ingested human insulin activates the insulin/IGF-1 signaling pathway in Anopheles stephensi and increases the susceptibility of these mosquitoes to Plasmodium falciparum. In other organisms, insulin can alter immune responsiveness through regulation of NF-κB transcription factors, critical elements for innate immunity that are also central to mosquito immunity. We show here that insulin signaling decreased expression of NF-κB-regulated immune genes in mosquito cells stimulated with either bacterial or malarial soluble products. Further, human insulin suppressed mosquito immunity through sustained phosphatidylinositol 3-kinase activation, since inhibition of this pathway led to decreased parasite development in the mosquito. Together, these data demonstrate that activation of the insulin/IGF-1 signaling pathway by ingested human insulin can alter NF-κB-dependent immunity, and ultimately the susceptibility, of mosquitoes to P. falciparum.
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, California, USA. npakpour@ucdavis.edu
authors.forename: Nazzy
authors.initials: N
authors.lastname: Pakpour
authors.forename: Vanessa
authors.initials: V
authors.lastname: Corby-Harris
authors.forename: Gabriel P
authors.initials: GP
authors.lastname: Green
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Smithers
authors.forename: Kong W
authors.initials: KW
authors.lastname: Cheung
authors.forename: Michael A
authors.initials: MA
authors.lastname: Riehle
authors.forename: Shirley
authors.initials: S
authors.lastname: Luckhart
mesh_terms: D000818:Animals; D000852:Anopheles / Q000187:drug effects* / Q000276:immunology* / Q000469:parasitology; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008070:Lipopolysaccharides; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010963:Plasmodium falciparum / Q000276:immunology*; D011401:Promoter Regions, Genetic; D015398:Signal Transduction
chemical_list: D007328:Insulin; D008070:Lipopolysaccharides; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases