Institute of Inflammation and Neurodegeneration, Health Campus Immunology, Infectiology and Inflammation (GC-I), Otto-von-Guericke University, Magdeburg, Germany.
Department of Microbial Immune Regulation, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Front Immunol. 2022 Jul 11;13:920658. doi: 10.3389/fimmu.2022.920658. eCollection 2022.
is a highly successful parasite capable of infecting all warm-blooded animals. The natural way of infection in intermediate hosts is the oral ingestion of parasite-contaminated water or food. In murine experimental models, oral infection () of mice with is applied to investigate mucosal and peripheral immune cell dynamics, whereas infection () is frequently used to study peripheral inflammation as well as immune cell - neuronal interaction in the central nervous system (CNS). However, the two infection routes have not yet been systematically compared along the course of infection. Here, C57BL/6 mice were infected or with a low dose of cysts, and the acute and chronic stages of infection were compared. A more severe course of infection was detected following challenge, characterized by an increased weight loss and marked expression of proinflammatory cytokines particularly in the CNS during the chronic stage. The elevated proinflammatory cytokine expression in the ileum was more prominent after challenge that continued following the acute phase in both or infected mice. This resulted in sustained microbial dysbiosis, especially after challenge, highlighted by increased abundance of pathobionts from the phyla proteobacteria and a reduction of beneficial commensal species. Further, we revealed that in the CNS of infected mice CD4 and CD8 T cells displayed higher IFNγ production in the chronic stage. This corresponded with an increased expression of C1q and CD68 in the CNS and reduced expression of genes involved in neuronal signal transmission. Neuroinflammation-associated synaptic alterations, especially PSD-95, VGLUT, and EAAT2 expression, were more pronounced in the cortex upon infection highlighting the profound interplay between peripheral inflammation and CNS homeostasis.
是一种非常成功的寄生虫，能够感染所有温血动物。中间宿主的自然感染途径是口服摄入受寄生虫污染的水或食物。在鼠类实验模型中，通过口服感染（）来研究黏膜和外周免疫细胞的动态变化，而感染（）则常用于研究外周炎症以及中枢神经系统（CNS）中的免疫细胞-神经元相互作用。然而，这两种感染途径在感染过程中尚未得到系统比较。在这里，C57BL/6 小鼠用低剂量的囊包虫感染或，比较了感染的急性和慢性阶段。与感染相比，感染后检测到更严重的感染过程，其特征是在慢性阶段体重减轻增加和促炎细胞因子的表达显著增加，尤其是在中枢神经系统中。感染后，感染或感染的小鼠的回肠中促炎细胞因子的表达更为明显，在急性阶段后持续存在。这导致了微生物失调的持续存在，特别是在感染后，表现为变形菌门和有益共生种减少的病原体丰度增加。此外，我们还揭示了在感染的小鼠中枢神经系统中，CD4 和 CD8 T 细胞在慢性阶段产生更高水平的 IFNγ。这与中枢神经系统中 C1q 和 CD68 的表达增加以及参与神经元信号转导的基因表达减少相对应。感染后皮层中与神经炎症相关的突触改变，特别是 PSD-95、VGLUT 和 EAAT2 的表达，更为明显，突出了外周炎症和中枢神经系统稳态之间的深刻相互作用。
