Dissection of the Molecular Interplay Between the Mosquito Innate Immune System, Gut Microbiome, and Pathogens
Embargo until
2014-12-01
Date
2013-09-23
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Publisher
Johns Hopkins University
Abstract
Malaria, caused by the Plasmodium parasite, affects approximately 3 billion people worldwide each year. The major vector for P. falciparum in sub-Saharan Africa is the female Anopheles gambiae mosquito. Given the lack of an effective vaccine against malaria and the increased resistance of this parasite to the current arsenal of drugs and of Anopheles mosquitoes to insecticides, the development of novel control strategies is crucial to reducing malaria transmission. Studies exploring the mosquito’s innate immune defense against Plasmodium as well as studies detailing the importance of the midgut microbiota in vector competence to pathogens may contribute towards the development of effective control strategies. In this thesis work, we have:
1. Conducted RNAi-based reverse genetic assays and high-throughput gene expression analysis to study the implication of the mosquito immune pathways in the response against the human malaria parasite Plasmodium falciparum. Additional infection and functional assays showed that the Imd immune pathway factor Caudal is an effective regulator of the anti-Plasmodium defense response in the Anopheles gambiae mosquito.
2. Studied the cross-colonization capacities between the midgut microbiota and the phylogenetically distinct mosquito species, Aedes aegypti and Anopheles gambiae. Investigating such interactions may provide insight in how to implement microbiota-based control strategies of different vector-borne diseases. Some bacterial isolates demonstrated the ability to cross-colonize the two mosquito hosts. However, some isolates demonstrated co-species adaptation rather than cross-colonization capacity.
This thesis work contributes to a better understanding of the mosquito immune system to the malaria parasite and microbiota-mosquito interactions.
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Keywords
Imd pathway, innate immunity, malaria, mosquito, Aedes, Anopheles, Plasmodium falciparum, microbiota