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Implication of mosquito peptidoglycan recognition proteins in immune regulation and anti-malarial defence.


Malaria still threatens human health and economic growth on a worldwide scale. The prevalence and mortality of this disease has been estimated with 300-500 million clinical cases and over 1 million deaths each year in tropical and sub-tropical regions of t he earth. The most affected area is sub-Saharan Africa where 90% of the infections occur. Malaria control has been hampered by the lack of a valid vaccine, and the development of resistance of Plasmodium spp. to drugs and of Anopheles spp. to insecticides. There is therefore a growing need for novel control measures, and research efforts have focused on the mosquito immune system. Malaria infection of the mosquito results in the activation of an immune response that contribute to the killing of Plasmodia. R ecognition of "non-self" leading to the activation of the known immune signalling pathways in the fruit fly have recently been shown to be mediated by members of a peptidoglycan recognition protein (PGRP) family that appears to represent the major pattern recognition receptors of its immune surveillance system. These immune responses are to a large extent responsible for the killing of parasites at the critical stages of their development in the mosquito, and only a fraction of ingested gametocytes will dev elop into ookinetes, of which only a small number will be forming oocysts, thus reducing the percentage of parasites able to localise in the salivary glands. The role of the mosquito PGRPs in regulating its immune system and activating anti-malarial defenc e mechanisms will be examined through the combination of reverse genetic and comparative transcriptomic approaches. The proposed project will contribute not only to our understanding of mosquito immune responses to Plasmodium, but will also lead the way to the unveiling of putative new targets (gene/molecules) for the development of novel malaria control measures.

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Piazza dell and apos;Universita 1

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