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

在撒哈拉以南非洲蠕虫流行的国家，怀孕期间慢性感染是常见的，可能导致不良的怀孕结果。有趣的是，最近的研究表明，妊娠期间慢性实验性感染曼氏血吸虫可导致后代的过敏性免疫反应受到抑制，这清楚地表明妊娠期间母体感染对后代的免疫系统有影响。在这种情况下，感染驱动的免疫反应在胎母界面（即胎盘）内被检测到，并同时显示出改变与维生素D相关的途径。炎症和胎盘内维生素D代谢之间的这种可能的相互作用可能暗示了感染相关信号如何从母亲转移到孩子身上的机制，并最终塑造了后代对过敏原甚至可能是感染或疫苗的反应能力。由于维生素D的稳态和相关因素，如维生素D受体（VDR），从来没有被彻底调查的感染和炎症的背景下，在怀孕和儿童期的免疫反应，我们建议研究是否也发生在人类感染寄生虫在加蓬的蠕虫流行区的胎儿母体串扰。为此，我们计划招募健康、寄生虫感染和蠕虫（非寄生虫）感染的孕妇及其新生儿。将测定母亲和后代的维生素D代谢及其相关因素和炎症参数以及免疫外周表型。我们将进一步研究这种感染是否会引起新生儿免疫系统发育和功能的变化。这些令人兴奋和具有挑战性的研究的结果将扩大我们对怀孕期间蠕虫介导的可能影响母亲和孩子的免疫功能以及随后对维生素D稳态的影响的了解。这些最终会对管理问题产生影响，例如适当的维生素D补充策略，怀孕期间使用抗蠕虫治疗，以及最终对受感染母亲的后代使用疫苗策略。最后，这些新的见解为更广泛地理解寄生虫进化的机制铺平了道路，这些机制不仅指导受感染的人类宿主的免疫反应，而且指导下一代的免疫反应。

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.