Abstract
Transmission of malaria is dependent on the successful completion of the Plasmodium lifecycle in the Anopheles vector. Major obstacles are encountered in the midgut tissue, where most parasites are killed by the mosquito's immune system. In the present study, DNA microarray analyses have been used to compare Anopheles gambiae responses to invasion of the midgut epithelium by the ookinete stage of the human pathogen Plasmodium falciparum and the rodent experimental model pathogen P. berghei. Invasion by P. berghei had a more profound impact on the mosquito transcriptome, including a variety of functional gene classes, while P. falciparum elicited a broader immune response at the gene transcript level. Ingestion of human malaria-infected blood lacking invasive ookinetes also induced a variety of immune genes, including several anti-Plasmodium factors. Twelve selected genes were assessed for effect on infection with both parasite species and bacteria using RNAi gene silencing assays, and seven of these genes were found to influence mosquito resistance to both parasite species. An MD2-like receptor, AgMDL1, and an immunolectin, FBN39, showed specificity in regulating only resistance to P. falciparum, while the antimicrobial peptide gambicin and a novel putative short secreted peptide, IRSP5, were more specific for defense against the rodent parasite P. berghei. While all the genes that affected Plasmodium development also influenced mosquito resistance to bacterial infection, four of the antimicrobial genes had no effect on Plasmodium development. Our study shows that the impact of P. falciparum and P. berghei infection on A. gambiae biology at the gene transcript level is quite diverse, and the defense against the two Plasmodium species is mediated by antimicrobial factors with both universal and Plasmodium-species specific activities. Furthermore, our data indicate that the mosquito is capable of sensing infected blood constituents in the absence of invading ookinetes, thereby inducing anti-Plasmodium immune responses.
Highlights
The transmission of the malarial parasite Plasmodium by the vector mosquito Anopheles gambiae is enabled by hematophagy, which is essential for egg production
To assess the impact of ookinete midgut invasion on the mosquito transcriptome, we compared gene expression in the gut and carcass tissues of mosquitoes that had fed on a wt Plasmodium-infected blood and those that had fed on blood infected with an invasion-incapable circumsporozoite- and TRAP-related protein (CTRP) knockout (CTRPÀ) Plasmodium mutants
Identical assays with wt Plasmodium and CTRP knockout mutants were conducted with P. falciparum and P. berghei, allowing comparison of the mosquito responses to midgut invasion by ookinetes of the two parasite species
Summary
The transmission of the malarial parasite Plasmodium by the vector mosquito Anopheles gambiae is enabled by hematophagy, which is essential for egg production. Within 24 h after ingestion of infected blood, the Plasmodium gametocytes are fertilized and develop into motile ookinetes, which invade and traverse the mosquito midgut epithelium to reach its basal side, where they develop into oocysts. One of the major barriers is the midgut epithelium, within which Plasmodium is attacked by the mosquito’s immune system. These defense reactions involve a variety of immune components that reduce the parasite population by several-fold and have mainly been described at the stage of ookinete invasion and beyond [1]. Recent studies have linked the A. gambiae NF-kappaB–like transcription factor REL2 and adaptor protein IMD to the defense against P. berghei and thereby established a role for the putative IMD pathway in anti-Plasmodium defense [8]. Plasmodium infection will affect a variety of other biological processes in addition to those linked to the immune response [7]
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