Malaria Parasites Co-opt Human Factor H to Prevent Complement-Mediated Lysis in the Mosquito Midgut

Research Center for Infectious Diseases, University of Würzburg, Josef-Schneider-Strasse 2/D15, 97080 Würzburg, Germany.
Cell host & microbe (Impact Factor: 12.33). 01/2013; 13(1):29-41. DOI: 10.1016/j.chom.2012.11.013
Source: PubMed


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.

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Available from: Gabriele Pradel, Oct 01, 2015
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    • " native human serum together with anti - FH an - tibodies , mosquitoes were rendered resistant as parasite numbers were effectively reduced to zero ( Simon et al . 2013 ) . Co - immunoprecipitation assays with anti - FH an - tibodies on protein extracts from activated gametes in native human serum identified PfGAP50 as a parasite receptor for FH ( Simon et al . 2013 ) . However , the au - thors suggest that there are additional unknown FH re - ceptors on the surface of the gametes as anti - PfGAP50 antibodies only reduced the infectivity to mosquitoes by 38 - 60% . This hypothesis is plausible as other pathogens including Streptococcus pyogenes and Borrelia burg - dorferi use more than one surface "
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    • "This delayed egress might provide the developing gamete with enough time to adapt to the mosquito midgut. Notably, we recently showed that following gametocyte activation the plasmodial transmembrane protein PfGAP50 relocates from the IMC to the PPM (Simon et al., 2013). Only after PfGAP50 is relocated to the PPM, the gametes exit the RBC. "
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