Research Center for Infectious Diseases, University of Würzburg, Josef-Schneider-Strasse 2/D15, 97080 Würzburg, Germany.
Cell Host Microbe. 2013 Jan 16;13(1):29-41. doi: 10.1016/j.chom.2012.11.013.
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.
人类补体是抵御感染的第一道防线，其中循环蛋白在微生物表面引发酶级联反应，导致吞噬作用和溶解。各种病原体通过与保护宿主细胞免受补体激活的调节蛋白结合来逃避补体识别。我们表明，疟原虫 Plasmodium falciparum 的新兴配子在传播到蚊子后结合宿主补体调节因子 H（FH），以防止被血液餐中的补体介导的溶解。人类补体在蚊子中肠中的活性约为进食后 1 小时。在此期间，配子表面蛋白 PfGAP50 与 FH 结合，并利用表面结合的 FH 使补体蛋白 C3b 失活。通过中和 FH 或阻断 PfGAP50 来消除 FH 介导的保护，会显著损害配子发生并抑制寄生虫向蚊子的传播。因此，疟原虫利用保护性宿主蛋白 FH 在蚊子中肠中逃避补体介导的溶解。
