Saskia Dewalick

Publications (3)11.3 Total impact

• Article: Schistosoma mansoni: the egg, biosynthesis of the shell and interaction with the host.

  Saskia deWalick, Aloysius G M Tielens, Jaap J van Hellemond
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  ABSTRACT: The schistosome eggshell is a hardened and tanned structure made from cross-linked proteins. It is synthesized within the female worm from many different kinds of proteins and glycoproteins. Once the egg is released in the circulation, the outer surface of the eggshell is exposed and hence a direct site of interaction between the parasite and the host. The major eggshell protein is p14, but about one third of the eggshell is made from common cellular proteins, some of which are known to be immunogenic. This has many consequences for parasite-host interactions. However, so far, the eggshell has gained little attention from researchers. We will discuss the structure of the eggshell and its role in granuloma formation, host factor binding and egg excretion.
  Experimental Parasitology 08/2011; 132(1):7-13. · 2.12 Impact Factor
• Article: The proteome of the insoluble Schistosoma mansoni eggshell skeleton.

  Saskia Dewalick, Michiel L Bexkens, Bas W M van Balkom, Ya-Ping Wu, Cornelis H Smit, Cornelis H Hokke, Philip G de Groot, Albert J R Heck, Aloysius G M Tielens, Jaap J van Hellemond
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  ABSTRACT: In schistosomiasis, the majority of symptoms of the disease is caused by the eggs that are trapped in the liver. These eggs elicit an immune reaction that leads to the formation of granulomas. The eggshell, which is a rigid insoluble structure built from cross-linked proteins, is the site of direct interaction between the egg and the immune system. However, the exact protein composition of the insoluble eggshell was previously unknown. To identify the proteins of the eggshell of Schistosoma mansoni we performed LC-MS/MS analysis, immunostaining and amino acid analysis on eggshell fragments. For this, eggshell protein skeleton was prepared by thoroughly cleaning eggshells in a four-step stripping procedure of increasing strength including urea and SDS to remove all material that is not covalently linked to the eggshell itself, but is part of the inside of the egg, such as Reynold's layer, von Lichtenberg's envelope and the miracidium. We identified 45 proteins of which the majority are non-structural proteins and non-specific for eggs, but are house-keeping proteins that are present in large quantities in worms and miracidia. Some of these proteins are known to be immunogenic, such as HSP70, GST and enolase. In addition, a number of schistosome-specific proteins with unknown function and no homology to any known annotated protein were found to be incorporated in the eggshell. Schistosome-specific glycoconjugates were also shown to be present on the eggshell protein skeleton. This study also confirmed that the putative eggshell protein p14 contributes largely to the eggshell. Together, these results give new insights into eggshell composition as well as eggshell formation. Those proteins that are present at the site and time of eggshell formation are incorporated in the cross-linked eggshell and this cross-linking does no longer occur when the miracidium starts secreting proteins.
  International journal for parasitology 01/2011; 41(5):523-32. · 3.39 Impact Factor
• Article: Cutting edge: conventional dendritic cells are the critical APC required for the induction of experimental cerebral malaria.

  Saskia deWalick, Fiona H Amante, Karli A McSweeney, Louise M Randall, Amanda C Stanley, Ashraful Haque, Rachel D Kuns, Kelli P A MacDonald, Geoff R Hill, Christian R Engwerda
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  ABSTRACT: Cerebral malaria (CM) is a serious complication of Plasmodium falciparum infection, causing significant morbidity and mortality among young children and nonimmune adults in the developing world. Although previous work on experimental CM has identified T cells as key mediators of pathology, the APCs and subsets therein required to initiate immunopathology remain unknown. In this study, we show that conventional dendritic cells but not plasmacytoid dendritic cells are required for the induction of malaria parasite-specific CD4+ T cell responses and subsequent experimental CM. These data have important implications for the development of malaria vaccines and the therapeutic management of CM.
  The Journal of Immunology 06/2007; 178(10):6033-7. · 5.79 Impact Factor