TY - JOUR
T1 - Two Mosquito LRR Proteins Function as Complement Control Factors in the TEP1-Mediated Killing of Plasmodium
AU - Fraiture, Malou
AU - Baxter, Richard H.G.
AU - Steinert, Stefanie
AU - Chelliah, Yogarany
AU - Frolet, Cécile
AU - Quispe-Tintaya, Wilber
AU - Hoffmann, Jules A.
AU - Blandin, Stéphanie A.
AU - Levashina, Elena A.
N1 - Funding Information:
The authors thank J. Soichot, L. Huck, and M.E. Moritz for help with the mosquito colony and parasite cultures and Doctor E. Marois for fruitful discussions and critical reading of the manuscript. R.H.G.B. and Y.C. thank Professor J. Deisenhofer for continuing support. This work was supported by grants from the Centre National de la Recherche Scientifique (UPR 9022 du CNRS), the Institut National de la Recherche Medicale (AVENIR Inserm to E.A.L.), the French Ministry of National Education and Research (Allocation de Recherche to M.F. and S.S., AMN to C.F.), the Schlumberger Foundation for Education and Research (FSER, E.A.L.), EMBO Young Investigator Program (E.A.L.), EC FP6 th Networks of Excellence “BioMalPar” (E.A.L. and J.A.H.), and the National Institutes of Health (2P01I44220-06A1 to J.A.H.). E.A.L. is an international research scholar of the Howard Hughes Medical Institute.
PY - 2009/3/19
Y1 - 2009/3/19
N2 - 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.
AB - 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.
KW - MICROBIO
KW - MOLIMMUNO
UR - http://www.scopus.com/inward/record.url?scp=61849177493&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=61849177493&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2009.01.005
DO - 10.1016/j.chom.2009.01.005
M3 - Article
C2 - 19286136
AN - SCOPUS:61849177493
SN - 1931-3128
VL - 5
SP - 273
EP - 284
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 3
ER -
