Functional characterization of the protease ClpQ in transgenic Plasmodium berghei in immunologically different murine hosts

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PaquetDurandTanja_2010_12_21.pdf (1.16 MB)

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2010

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DOI:
http://dx.doi.org/10.22029/jlupub-11655

Abstract

The protease ClpQ, encoded by the plasmodial gene hslV (PB000649.02.0), is a threonine peptidase, expressed by plasmodia during the late blood stages. Due to its highly conserved sequence among Plasmodium spp., hslV appears to play a fundamental role in plasmodial cell metabolism. This thesis investigates its function by generation and phenotypic characterization of transgenic, hslV-deficient Plasmodium berghei parasites. hslV-deficient parasites showed a substantial growth retardation of the blood stages, which was partially reversed when MyD88-deficient mice were used as a host organism.An explanation for this phenomenon could be a linkage of hslV-mediated signaling of the parasite and Toll-like receptor signaling of the murine host, which leads to improved growth conditions for the invading parasite. These beneficial environment is probably not provided in hslV-deficient parasites or in a MyD88-deficient-host explaining the lower parasite growth rates under those conditions. How these host-parasite-interactions are mediated, is subject of further investigations.In summary, the obtained results suggest that the protease ClpQ may be involved in the modulation of the host s innate immune response during an infection with Plasmodium berghei, which suggests that ClpQ is a candidate for a plasmodial virulence factor. Its absence in the mammalian host makes ClpQ an attractive target for future interventional approaches. Further research to characterize related molecular pathways is needed to clarify its role during the innate immune response especially in view of future vaccine development strategies.

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