TY - JOUR
T1 - Malaria parasites co-opt human factor h to prevent complement-mediated lysis in the mosquito midgut
AU - Simon, Nina
AU - Lasonder, Edwin
AU - Scheuermayer, Matthias
AU - Kuehn, Andrea
AU - Tews, Sabrina
AU - Fischer, Rainer
AU - Zipfel, Peter F.
AU - Skerka, Christine
AU - Pradel, Gabriele
N1 - Funding information: We thank Ludmilla Sologub and Andrea Hartmann for excellent technical assistance, the Nijmegen Proteomics Facility (Radboud University Nijmegen) for usage of the MS instrumentation, and the team of G. Krohne (University of Würzburg) for support with electron microscopy. This work was funded by the Collaborative Research Centre SFB479, the Priority Programme SPP1580, and an Emmy-Noether grant of the Deutsche Forschungsgemeinschaft (to G.P.). The work was additionally supported by the MALSIG consortium of the EU 7th Framework Programme (to G.P.). N.S. received a fellowship from the program for female scientists of the University of Würzburg. A.K. was an associated member of the BioMedTec International Graduate School of Science “Lead Structures of Cell Function” of the Elite Network Bavaria.
PY - 2013/1/16
Y1 - 2013/1/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84872585440&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2012.11.013
DO - 10.1016/j.chom.2012.11.013
M3 - Article
AN - SCOPUS:84872585440
SN - 1931-3128
VL - 13
SP - 29
EP - 41
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 1
ER -