Search PubMed⌕ Search

Biomedical subjects

Stéphanie Blandin

Publications and source records attributed to Stéphanie Blandin.

6 recordsLinked to original sources

Boosting NF-kappaB-dependent basal immunity of Anopheles gambiae aborts development of Plasmodium berghei.

Anopheles gambiae, the major vector for the protozoan malaria parasite Plasmodium falciparum, mounts powerful antiparasitic responses that cause marked parasite loss during midgut invasion. Here, we showed that these antiparasitic defenses were composed of pre- and postinvasion phases and that the preinvasion phase was predominantly regulated by Rel1 and Rel2 members of the NF-kappaB transcription factors. Concurrent silencing of Rel1 and Rel2 decreased the basal expression of the major antiparasitic genes TEP1 and LRIM1 and abolished resistance of Anopheles to the rodent malaria parasite P. berghei. Conversely, depletion of a negative regulator of Rel1, Cactus, prior to infection, enhanced the basal expression of TEP1 and of other immune factors and completely prevented parasite development. Our findings uncover the crucial role of the preinvasion defense in the elimination of parasites, which is at least in part based on circulating blood molecules.

Animals↗

Mosquito immune responses against malaria parasites.

Anopheline mosquitoes are the major vectors of human malaria. Mosquito-parasite interactions are a critical aspect of disease transmission and a potential target for malaria control. Mosquitoes vary in their innate ability to support development of the malaria parasite, but the molecular mechanisms that determine vector competence are poorly understood. This area of research has been revolutionized by recent advances in the mosquito genome characterization and by the development of new tools for functional gene analysis.

Animals↗

Thioester-containing proteins and insect immunity.

Here, we discuss the role of thioester-containing proteins in innate immune responses of insects. TEPs are represented by multi-member families both in the fruitfly, Drosophila melanogaster, and in the mosquito, Anopheles gambiae. Phylogenetic analysis of the family suggests that in these two dipteran species evolution of TEPs followed independent scenarios as a result of specific adaptation to distinct ecological environments. Research on these two relatively simple model systems, which lack adaptive immunity, may provide new insights into the evolutionary origins and functions of this important protein family.

Animals↗

Silencing of Toll pathway components by direct injection of double-stranded RNA into Drosophila adult flies.

Double-stranded RNA (dsRNA) gene interference is an efficient method to silence gene expression in a sequence-specific manner. Here we show that the direct injection of dsRNA can be used in adult Drosophila flies to disrupt function of endogenous genes in vivo. As a proof of principle, we have used this method to silence components of a major signaling cascade, the Toll pathway, which controls fruit fly resistance to fungal and Gram-positive bacterial infections. We demonstrate that the knockout is efficient only if dsRNA is injected in 4- or more day-old flies and that it lasts for at least 1 week. Furthermore, we report dsRNA-based epistatic gene analysis via injection of a mixture of two dsRNAs and propose that injection of dsRNA represents a powerful method for rapid functional analysis of genes in Drosophila melanogaster adults, particularly of those whose mutations are lethal during development.

Animals↗

Reverse genetics in the mosquito Anopheles gambiae: targeted disruption of the Defensin gene.

Anopheles gambiae, the major vector of human malaria parasite, is an important insect model to study vector-parasite interactions. Here, we developed a simple in vivo double-stranded RNA (dsRNA) knockout approach to determine the function of the mosquito antimicrobial peptide gene Defensin. We injected dsRNA into adults and observed efficient and reproducible silencing of Defensin. Analysis of the knockdown phenotype revealed that this peptide is required for the mosquito antimicrobial defense against Gram-positive bacteria. In contrast, in mosquitoes infected by Plasmodium berghei, no loss of mosquito viability and no significant effect on the development and morphology of the parasite midgut stages were observed in the absence of Defensin. We conclude that this peptide is not a major antiparasitic factor in A. gambiae in vivo. Our results open new perspectives for the study of mosquito gene function in vivo and provide a basis for genome-scale systematic functional screens by targeted gene silencing.

Animals↗