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Originally published In Press as doi:10.1074/jbc.M510957200 on January 31, 2006

J. Biol. Chem., Vol. 281, Issue 13, 8426-8435, March 31, 2006
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Regulation of Lipid Metabolism Genes, Lipid Carrier Protein Lipophorin, and Its Receptor during Immune Challenge in the Mosquito Aedes aegypti*

Hyang-Mi Cheon, Sang Woon Shin, Guowu Bian, Jong-Hwa Park, and Alexander S. Raikhel1

From the Center for Disease-Vector Research, Department of Entomology and the Institute for Integrative Genome Biology, University of California, Riverside, California 92521

In the mosquito Aedes aegypti, the expression of two fat body genes involved in lipid metabolism, a lipid carrier protein lipophorin (Lp) and its lipophorin receptor (LpRfb), was significantly increased after infections with Gram (+) bacteria and fungi, but not with Gram (–) bacteria. The expression of these genes was enhanced after the infection with Plasmodium gallinaceum. RNA interference (RNAi) knockdown of Lp strongly restricted the development of Plasmodium oocysts, reducing their number by 90%. In Vg-{Delta}REL1-A transgenic mosquitoes, with gain-of-function phenotype of Toll/REL1 immune pathway activated after blood feeding, both the Lp and LpRfb genes were overexpressed independently of septic injury. The same phenotype was observed in the mosquitoes with RNAi knockdown of Cactus, an I{kappa}B inhibitor in the Toll/REL1 pathway. These results showed that, in the mosquito fat body, both Lp and LpRfb gene expression were regulated by the Toll/REL1 pathway during immune induction by pathogen and parasite infections. Indeed, the proximal region of the LpRfb promoter contained closely linked binding motifs for GATA and NF-{kappa}B transcription factors. Transfection and in vivo RNAi knockdown experiments showed that the bindings of both GATA and NF-{kappa}B transcription factors to the corresponding motif were required for the induction of the LpRfb gene. These findings suggest that lipid metabolism is involved in the mosquito systemic immune responses to pathogens and parasites.


Received for publication, October 6, 2005 , and in revised form, January 27, 2006.

* This work was supported by National Institutes of Health Grants R37-AI24716 and RO1-AI052492 (to A. S. R.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 To whom correspondence should be addressed: Center for Disease-Vector Research, Dept. of Entomology and the Institute for Integrative Genome Biology, University of California, Riverside, CA 92521. Tel.: 951-787-2129; Fax: 951-787-2130; E-mail: alexander.raikhel{at}ucr.edu.


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