Institute of Parasitology, McGill University (Macdonald Campus), 21,111 Lakeshore Road, Ste-Anne de Bellevue, QC, H9X 3V9, Canada.
Department of Animal Science, McGill University (Macdonald Campus), 21,111 Lakeshore Road, Ste-Anne de Bellevue, QC, H9X 3V9, Canada.
Sci Rep. 2021 Nov 11;11(1):22082. doi: 10.1038/s41598-021-01510-0.
Intestinal nematode infections common during pregnancy have recently been shown to have impacts that extend to their uninfected offspring including altered brain gene expression. If maternal immune signals reach the neonatal brain, they might alter neuroimmune development. We explored expression of genes associated with four distinct types of T cells (Th1, Th2, Th17, Treg) and with leukocyte transendothelial migration and endocytosis transport across the blood-brain barrier (BBB) in the postnatal brain of offspring of nematode-infected mice, through secondary analysis of a whole brain gene expression database. Th1/Th17 expression was lowered by maternal infection as evidenced by down-regulated expression of IL1β, Th1 receptors and related proteins, and of IL22 and several Th17 genes associated with immunopathology. In contrast, Th2/Treg related pathways were upregulated as shown by higher expression of IL4 and TGF-β family genes. Maternal infection also upregulated expression of pathways and integrin genes involved in transport of leukocytes in between endothelial cells but downregulated endosome vesicle formation related genes that are necessary for endocytosis of immunoglobulins across the BBB. Taken together, pup brain gene expression indicates that maternal nematode infection enhanced movement of leukocytes across the neonatal BBB and promoted a Th2/Treg environment that presumably minimizes the proinflammatory Th1 response in the pup brain.
肠道寄生虫感染在怀孕期间很常见，最近的研究表明，它们的影响不仅局限于未感染的后代，还包括改变大脑基因表达。如果母体的免疫信号到达新生儿的大脑，它们可能会改变神经免疫的发育。我们通过对整个大脑基因表达数据库的二次分析，探索了与四种不同类型的 T 细胞（Th1、Th2、Th17、Treg）以及白细胞穿过血脑屏障（BBB）的内皮迁移和内吞转运相关的基因在感染肠道寄生虫的母鼠后代出生后大脑中的表达。母源性感染降低了 Th1/Th17 的表达，这表现在白细胞介素 1β（IL1β）、Th1 受体和相关蛋白、IL22 以及几种与免疫病理学相关的 Th17 基因的下调表达上。相比之下，Th2/Treg 相关途径被上调，这表现为白细胞介素 4（IL4）和 TGF-β 家族基因的高表达。母体感染还上调了参与白细胞在内皮细胞之间转运的途径和整合素基因，但下调了内体小泡形成相关基因，这些基因对于免疫球蛋白穿过 BBB 的内吞作用是必需的。综上所述，幼鼠大脑的基因表达表明，母体肠道寄生虫感染增强了白细胞穿过新生幼鼠 BBB 的运动，并促进了 Th2/Treg 环境的形成，这可能最大限度地减少了幼鼠大脑中的促炎 Th1 反应。
