Two mosquito LRR proteins function as complement control factors in the TEP1-mediated killing of Plasmodium.
Plasmodium development within Anopheles mosquitoes is a vulnerable step in the parasite transmission cycle, and targeting this step represents a promising strategy for malaria control. The thioester-containing complement-like protein TEP1 and two leucine-rich repeat (LRR) proteins, LRIM1 and APL1, have been identified as major mosquito factors that regulate parasite loads. Here, we show that LRIM1 and APL1 are required for binding of TEP1 to parasites. RNAi silencing of the LRR-encoding genes results in deposition of TEP1 on Anopheles tissues, thereby depleting TEP1 from circulation in the hemolymph and impeding its binding to Plasmodium. LRIM1 and APL1 not only stabilize circulating TEP1, they also stabilize each other prior to their interaction with TEP1. Our results indicate that three major antiparasitic factors in mosquitoes jointly function as a complement-like system in parasite killing, and they reveal a role for LRR proteins as complement control factors.
Fraiture
Malou
M
UPR 9022 CNRS, AVENIR group Inserm, Institut de Biologie Moléculaire et Cellulaire, 15 rue René Descartes, 67084 Strasbourg, France.
Baxter
Richard H G
RH
Steinert
Stefanie
S
Chelliah
Yogarany
Y
Frolet
Cécile
C
Quispe-Tintaya
Wilber
W
Hoffmann
Jules A
JA
Blandin
Stéphanie A
SA
Levashina
Elena A
EA
D000818:Animals; D000852:Anopheles / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D006458:Hemolymph / Q000276:immunology; D007155:Immunologic Factors / Q000276:immunology* / Q000378:metabolism; D008954:Models, Biological; D010961:Plasmodium / Q000276:immunology*; D011485:Protein Binding; D011506:Proteins / Q000276:immunology / Q000378:metabolism
D007155:Immunologic Factors; D011506:Proteins; D003165:Complement System Proteins