Assessing the effect of maternal helminth infection on Vitamin D regulation and on the immune system of the infant (HELMVIT)

点击翻译按钮获取中文摘要

In countries of sub-Saharan Africa endemic for helminths, chronic infection during pregnancy is a common occurrence and can result in adverse pregnancy outcomes. Interestingly, it was recently shown that chronic experimental infection with the helminth Schistosoma mansoni during pregnancy can lead to suppressed allergic immune responses in offspring, demonstrating clearly that maternal infection during pregnancy has an influence on the immune system of the offspring. In this context, infection-driven immune responses were detected within the fetomaternal interface, i.e. the placenta, and were simultaneously shown to alter pathways related to vitamin D. This possible interaction between inflammation and Vitamin D metabolism within the placenta could hint towards a mechanism of how infection related signals are transferred from the mother to the child and eventually shape the offspring’s capacity to react to allergens and possibly even infections or vaccines. Since vitamin D homeostasis and related factors, such as the vitamin D receptor (VDR), have never been investigated thoroughly in the context of infections and inflammation during pregnancy and childhood immune responses, we propose to study whether this fetomaternal crosstalk also occurs in humans infected with schistosomes within a helminth-endemic area in Gabon. For this purpose we plan to recruit healthy, schistosome-infected and helminth (non-schistosome) infected pregnant women and their newborns. Vitamin D metabolism and its related factors and inflammation parameters as well as immunological peripheral phenotype of the mother and offspring will be determined. We will furthermore investigate whether such infections induce changes in the development and function of the immune system of newborns. The results of these exciting and challenging studies will expand our knowledge of possible helminth-mediated effects during pregnancy on the immune function in the mother and the child and subsequent effects on vitamin D homeostasis. These would eventually have consequences regarding management issues such as adequate vitamin D supplementation strategies, the usage of anti-helminthic therapy during pregnancy, and eventually vaccine strategies in offspring from infected mothers. Finally, these new insights pave the way towards a broader understanding of mechanisms that parasites have evolved to instruct not only the immune reactions from its infected human host, but also those in the next generation.