The role of NF-kappaB factor REL2 in the Aedes aegypti immune response.
Mosquitoes transmit numerous diseases that continue to be an enormous burden on public health worldwide. Transgenic mosquitoes impervious to vector-borne pathogens, in concert with vector control and drug and vaccine development, comprise an arsenal of means anticipated to defeat mosquito-spread diseases in the future. Mosquito transgenesis allows tissue-specific manipulation of their major immune pathways and enhances the ability to study mosquito-pathogen interactions. Here, we report the generation of two independent transgenic strains of Aedes aegypti overexpressing the NF-?B transcriptional factor REL2, a homologue of Drosophila Relish, which is shown to be under the control of the vitellogenin promoter in the mosquito fat body after a blood meal. We show that this REL2 overexpression in the fat body results in transcriptional activation of Defensins A, C, and D, and Cecropins A and N, as well as translation and secretion of Defensin A protein into the hemolymph. We also demonstrate that induction of REL2 results in the increased resistance of the mosquito to tested Gram-negative and Gram-positive bacteria. Importantly, induction of transgenic REL2 leads to the significant decrease in susceptibility of A. aegypti to Plasmodium gallinaceum infection. Consistently, RNAi knockdown of REL2 in wild-type mosquitoes results in a delay in Defensin A and Cecropin A expression in response to infection and in increased susceptibility to both bacteria and P. gallinaceum. Moreover, our transgenic assays demonstrate that the N-terminus of the mosquito REL2, which includes the His/Gln-rich and serine-rich regions, plays a role in its transactivation properties.
Antonova
Yevgeniya
Y
Graduate Program in Biochemistry and Molecular Biology, University of California, Riverside, CA 92521, USA.
Alvarez
Kanwal S
KS
Kim
Yu Jung
YJ
Kokoza
Vladimir
V
Raikhel
Alexander S
AS
D000330:Aedes / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000469:parasitology; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000276:immunology; D001419:Bacteria; D023082:Defensins / Q000235:genetics / Q000276:immunology; D005216:Fat Body / Q000276:immunology; D015870:Gene Expression; D054884:Host-Pathogen Interactions / Q000276:immunology*; D019476:Insect Proteins / Q000235:genetics / Q000276:immunology*; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology*; D010964:Plasmodium gallinaceum / Q000502:physiology; D015533:Transcriptional Activation
D023181:Antimicrobial Cationic Peptides; D023082:Defensins; D019476:Insect Proteins; D016328:NF-kappa B; C031161:cecropin A