title: Two insulin-like peptides differentially regulate malaria parasite infection in the mosquito through effects on intermediary metabolism.
abstract: Insulin-like peptides (ILPs) play important roles in growth and metabolic homeostasis, but have also emerged as key regulators of stress responses and immunity in a variety of vertebrates and invertebrates. Furthermore, a growing literature suggests that insulin signaling-dependent metabolic provisioning can influence host responses to infection and affect infection outcomes. In line with these studies, we previously showed that knockdown of either of two closely related, infection-induced ILPs, ILP3 and ILP4, in the mosquito Anopheles stephensi decreased infection with the human malaria parasite Plasmodium falciparum through kinetically distinct effects on parasite death. However, the precise mechanisms by which ILP3 and ILP4 control the response to infection remained unknown. To address this knowledge gap, we used a complementary approach of direct ILP supplementation into the blood meal to further define ILP-specific effects on mosquito biology and parasite infection. Notably, we observed that feeding resulted in differential effects of ILP3 and ILP4 on blood-feeding behavior and P. falciparum development. These effects depended on ILP-specific regulation of intermediary metabolism in the mosquito midgut, suggesting a major contribution of ILP-dependent metabolic shifts to the regulation of infection resistance and parasite transmission. Accordingly, our data implicate endogenous ILP signaling in balancing intermediary metabolism for the host response to infection, affirming this emerging tenet in host-pathogen interactions with novel insights from a system of significant public health importance.
authors: Department of Medical Microbiology and Immunology, University of California Davis, Davis, CA, U.S.A.
authors: Jose E
authors: JE
authors: Pietri
authors: Department of Medical Microbiology and Immunology, University of California Davis, Davis, CA, U.S.A.
authors: Nazzy
authors: N
authors: Pakpour
authors: Department of Molecular Biosciences, University of California Davis, Davis, CA, U.S.A.
authors: Eleonora
authors: E
authors: Napoli
authors: Department of Molecular Biosciences, University of California Davis, Davis, CA, U.S.A.
authors: Gyu
authors: G
authors: Song
authors: Department of Medical Microbiology and Immunology, University of California Davis, Davis, CA, U.S.A.
authors: Eduardo
authors: E
authors: Pietri
authors: Department of Medical Microbiology and Immunology, University of California Davis, Davis, CA, U.S.A.
authors: Rashaun
authors: R
authors: Potts
authors: Department of Medical Microbiology and Immunology, University of California Davis, Davis, CA, U.S.A.
authors: Kong W
authors: KW
authors: Cheung
authors: Department of Medical Microbiology and Immunology, University of California Davis, Davis, CA, U.S.A.
authors: Gregory
authors: G
authors: Walker
authors: Department of Entomology, University of Arizona, Tucson, AZ, U.S.A.
authors: Michael A
authors: MA
authors: Riehle
authors: Department of Medical Microbiology and Immunology, University of California Davis, Davis, CA, U.S.A.
authors: Hannah
authors: H
authors: Starcevich
authors: Department of Molecular Biosciences, University of California Davis, Davis, CA, U.S.A. Medical Investigations of Neurodevelopmental Disorders (M.I.N.D.) Institute, University of California Davis, Sacramento, CA, U.S.A.
authors: Cecilia
authors: C
authors: Giulivi
authors: Department of Entomology and Nematology, University of California, Davis, CA, U.S.A.
authors: Edwin E
authors: EE
authors: Lewis
authors: Department of Medical Microbiology and Immunology, University of California Davis, Davis, CA, U.S.A.
authors: Shirley
authors: S
authors: Luckhart
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D015153:Blotting, Western; D005247:Feeding Behavior / Q000502:physiology; D005260:Female; D054884:Host-Pathogen Interactions; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000737:chemistry*; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D010963:Plasmodium falciparum / Q000187:drug effects / Q000472:pathogenicity
chemical_list: D019476:Insect Proteins; D007328:Insulin; D010455:Peptides
keywords: Anopheles; ILP; Plasmodium falciparum; insulin; malaria; mosquito