Parasitic worms of the genus, Schistosoma, infect millions of people mainly in the tropics and can cause serious morbidity. Human schistosoma infection is often associated with strong T helper 2... Show moreParasitic worms of the genus, Schistosoma, infect millions of people mainly in the tropics and can cause serious morbidity. Human schistosoma infection is often associated with strong T helper 2 polarized immune responses as well as immunehyporesponsiveness. Dendritic cells play a central role in sensing of pathogens and generation of appropriate immune responses against these pathogens. This thesis describes that human schistosoma infection suppresses phenotype and T cell polarizing capacity of dendritic cells present in blood of these subjects. Furthermore, in vitro studies identified molecular markers in dendritic cells that can be used to predict whether these cells will induce T helper 1 or 2 responses following exposure to Th1-polarizing bacterial extracts or Th2- skewing lipids derived from schistosoma worms. Finally, the identification of the major Th2-polarizing component secreted by schistosoma eggs and the molecular mechanisms through which this factor instructs dendritic cells to drive this response is described. Taken together, these studies provide new insights in the molecular interplay between dendritic cells and schistosomes and as such in the cellular and molecular mechanisms behind shaping of T helper 2 immune responses and/or immunehyporesponsiveness observed during these parasitic worm infections. Show less
