Two Mosquito LRR Proteins Function as Complement Control Factors in the TEP1-Mediated Killing of Plasmodium

Malou Fraiture, Richard H G Baxter, Stefanie Steinert, Yogarany Chelliah, Cécile Frolet, Wilber Quispe-Tintaya, Jules A. Hoffmann, Stéphanie A. Blandin, Elena A. Levashina

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)273-284
Number of pages12
JournalCell Host and Microbe
Volume5
Issue number3
DOIs
StatePublished - Mar 19 2009
Externally publishedYes

Fingerprint

Plasmodium
Culicidae
Parasites
Anopheles
Parasite Load
Antiparasitic Agents
Hemolymph
RNA Interference
Leucine
Malaria
Complement System Proteins
Genes
leucine-rich repeat proteins

Keywords

  • MICROBIO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

Fraiture, M., Baxter, R. H. G., Steinert, S., Chelliah, Y., Frolet, C., Quispe-Tintaya, W., ... Levashina, E. A. (2009). Two Mosquito LRR Proteins Function as Complement Control Factors in the TEP1-Mediated Killing of Plasmodium. Cell Host and Microbe, 5(3), 273-284. https://doi.org/10.1016/j.chom.2009.01.005

Two Mosquito LRR Proteins Function as Complement Control Factors in the TEP1-Mediated Killing of Plasmodium. / Fraiture, Malou; Baxter, Richard H G; Steinert, Stefanie; Chelliah, Yogarany; Frolet, Cécile; Quispe-Tintaya, Wilber; Hoffmann, Jules A.; Blandin, Stéphanie A.; Levashina, Elena A.

In: Cell Host and Microbe, Vol. 5, No. 3, 19.03.2009, p. 273-284.

Research output: Contribution to journalArticle

Fraiture, M, Baxter, RHG, Steinert, S, Chelliah, Y, Frolet, C, Quispe-Tintaya, W, Hoffmann, JA, Blandin, SA & Levashina, EA 2009, 'Two Mosquito LRR Proteins Function as Complement Control Factors in the TEP1-Mediated Killing of Plasmodium', Cell Host and Microbe, vol. 5, no. 3, pp. 273-284. https://doi.org/10.1016/j.chom.2009.01.005
Fraiture, Malou ; Baxter, Richard H G ; Steinert, Stefanie ; Chelliah, Yogarany ; Frolet, Cécile ; Quispe-Tintaya, Wilber ; Hoffmann, Jules A. ; Blandin, Stéphanie A. ; Levashina, Elena A. / Two Mosquito LRR Proteins Function as Complement Control Factors in the TEP1-Mediated Killing of Plasmodium. In: Cell Host and Microbe. 2009 ; Vol. 5, No. 3. pp. 273-284.
@article{19ce433c185645ac968040b5cb950d08,
title = "Two Mosquito LRR Proteins Function as Complement Control Factors in the TEP1-Mediated Killing of Plasmodium",
abstract = "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.",
keywords = "MICROBIO, MOLIMMUNO",
author = "Malou Fraiture and Baxter, {Richard H G} and Stefanie Steinert and Yogarany Chelliah and C{\'e}cile Frolet and Wilber Quispe-Tintaya and Hoffmann, {Jules A.} and Blandin, {St{\'e}phanie A.} and Levashina, {Elena A.}",
year = "2009",
month = "3",
day = "19",
doi = "10.1016/j.chom.2009.01.005",
language = "English (US)",
volume = "5",
pages = "273--284",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "3",

}

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.

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

VL - 5

SP - 273

EP - 284

JO - Cell Host and Microbe

JF - Cell Host and Microbe

SN - 1931-3128

IS - 3

ER -