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: Nina Simon, Edwin Lasonder, Matthias Scheuermayer, Andrea Kuehn, Sabrina Tews, Rainer Fischer, Peter F Zipfel, Christine Skerka, Gabriele Pradel
• Journal: Cell host & microbe (Cell Host Microbe) Vol. 13 Issue 1 Pg. 29-41 (Jan 16 2013) ISSN: 1934-6069 [Electronic] United States
• PMID: 23332154 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Complement C3
• Membrane Proteins
• glideosome-associated protein 50, Plasmodium falciparum
• Complement Factor H

Topics

• Animals
• Complement C3 (immunology)
• Complement Factor H (immunology)
• Culicidae (immunology, parasitology, physiology)
• Digestive System (immunology, parasitology)
• Female
• Germ Cells (growth & development, immunology)
• Host-Parasite Interactions
• Humans
• Insect Vectors (immunology, parasitology, physiology)
• Malaria, Falciparum (parasitology)
• Membrane Proteins (genetics, metabolism)
• Plasmodium falciparum (growth & development, immunology, physiology)