The Roslin Institute & Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, EH25 9RG, United Kingdom.
Wellcome Trust Centre for Molecular Parasitology, Institute for Infection, Immunity and Inflammation, Sir Graeme Davies Building, 120 University Place, Glasgow, G12 8TA, United Kingdom.
Sci Rep. 2019 Apr 30;9(1):6674. doi: 10.1038/s41598-019-42900-9.
The early replication of some orally-acquired prion strains upon stromal-derived follicular dendritic cells (FDC) within the small intestinal Peyer's patches is essential to establish host infection, and for the disease to efficiently spread to the brain. Factors that influence the early accumulation of prions in Peyer's patches can directly influence disease pathogenesis. The host's immune response to a gastrointestinal helminth infection can alter susceptibility to co-infection with certain pathogenic bacteria and viruses. Here we used the natural mouse small intestine-restricted helminth pathogen Heligmosomoides polygyrus to test the hypothesis that pathology specifically within the small intestine caused by a helminth co-infection would influence oral prion disease pathogenesis. When mice were co-infected with prions on d 8 after H. polygyrus infection the early accumulation of prions within Peyer's patches was reduced and survival times significantly extended. Natural prion susceptible hosts such as sheep, deer and cattle are regularly exposed to gastrointestinal helminth parasites. Our data suggest that co-infections with small intestine-restricted helminth pathogens may be important factors that influence oral prion disease pathogenesis.
某些经口摄入的朊病毒株在小肠派尔集合淋巴结中的基质衍生滤泡树突状细胞（FDC）中的早期复制对于建立宿主感染以及使疾病有效地传播到大脑至关重要。影响派尔集合淋巴结中朊病毒早期积累的因素会直接影响疾病的发病机制。宿主对胃肠道寄生虫感染的免疫反应可以改变对某些致病性细菌和病毒的共感染的易感性。在这里，我们使用天然的局限于小肠的寄生虫病原体旋毛虫来检验以下假说：寄生虫共感染引起的小肠特定部位的病理变化会影响经口朊病毒病的发病机制。当在感染旋毛虫后第 8 天用朊病毒对小鼠进行共感染时，派尔集合淋巴结中朊病毒的早期积累减少，并且存活时间显著延长。绵羊、鹿和牛等天然易感染朊病毒的宿主经常会接触胃肠道寄生虫。我们的数据表明，与局限于小肠的寄生虫病原体的共感染可能是影响经口朊病毒病发病机制的重要因素。
