title: Malaria parasites co-opt human factor H to prevent complement-mediated lysis in the mosquito midgut.
abstract: Human complement is a first line defense against infection in which circulating proteins initiate an enzyme cascade on the microbial surface that leads to phagocytosis and lysis. Various pathogens evade complement recognition by binding to regulator proteins that protect host cells from complement activation. We show that emerging gametes of the malaria parasite Plasmodium falciparum bind the host complement regulator factor H (FH) following transmission to the mosquito to protect from complement-mediated lysis by the blood meal. Human complement is active in the mosquito midgut for approximately 1 hr postfeeding. During this period, the gamete surface protein PfGAP50 binds to FH and uses surface-bound FH to inactivate the complement protein C3b. Loss of FH-mediated protection, either through neutralization of FH or blockade of PfGAP50, significantly impairs gametogenesis and inhibits parasite transmission to the mosquito. Thus, Plasmodium co-opts the protective host protein FH to evade complement-mediated lysis within the mosquito midgut.
authors: Research Center for Infectious Diseases, University of Würzburg, Josef-Schneider-Strasse 2/D15, 97080 Würzburg, Germany.
authors: Nina
authors: N
authors: Simon
authors: Edwin
authors: E
authors: Lasonder
authors: Matthias
authors: M
authors: Scheuermayer
authors: Andrea
authors: A
authors: Kuehn
authors: Sabrina
authors: S
authors: Tews
authors: Rainer
authors: R
authors: Fischer
authors: Peter F
authors: PF
authors: Zipfel
authors: Christine
authors: C
authors: Skerka
authors: Gabriele
authors: G
authors: Pradel
mesh_terms: D000818:Animals; D003176:Complement C3 / Q000276:immunology*; D017242:Complement Factor H / Q000276:immunology*; D009033:Culicidae / Q000276:immunology* / Q000469:parasitology / Q000502:physiology; D004064:Digestive System / Q000276:immunology / Q000469:parasitology; D005260:Female; D005854:Germ Cells / Q000254:growth & development / Q000276:immunology; D006790:Host-Parasite Interactions; D006801:Humans; D007303:Insect Vectors / Q000276:immunology* / Q000469:parasitology / Q000502:physiology; D016778:Malaria, Falciparum / Q000469:parasitology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology* / Q000502:physiology
chemical_list: D003176:Complement C3; D008565:Membrane Proteins; C509919:glideosome-associated protein 50, Plasmodium falciparum; D017242:Complement Factor H