Section of Infection Biology, Department of Functional Bioscience, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan.
Section of Oral Implantology, Department of Oral Rehabilitation, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan.
Exp Anim. 2020 Apr 24;69(2):250-260. doi: 10.1538/expanim.19-0156. Epub 2020 Jan 31.
Maternal immune activation (MIA) by an infection is considered to be an important environmental factor of fetal brain development. Recent animal model on MIA induced by polyinosinic:polycytidylic acid, a mimic of viral infection, demonstrates that maternal IL-17A signaling is required for the development of autism spectrum disorder (ASD)-like behaviors of offspring. However, there is little information on bacterial infection. In this study, we aim to elucidate the influence of MIA induced by lipopolysaccharide (LPS) to mimic a bacterial infection on fetal brain development. We demonstrated that LPS-induced MIA promoted ASD-like behaviors in mouse offspring. We further found that LPS exposure induced acute phase immune response: elevation of serum IL-17A levels in MIA mothers, upregulation of Il17a mRNA expression and increase of IL-17A-producing γδ T cells in the uterus, and upregulation of Il17ra mRNA expression in the fetal brain. Blocking of IL-17A in LPS-induced MIA ameliorated ASD-like behaviors in offspring. Our data suggest that bacterial-induced maternal IL-17A pathway promotes ASD-like behaviors in offspring.
母体免疫激活（MIA）由感染被认为是胎儿大脑发育的重要环境因素。最近的动物模型研究表明，多聚肌苷酸：多聚胞苷酸（一种病毒感染的模拟物）诱导的 MIA 中，母体白细胞介素-17A（IL-17A）信号通路对于后代自闭症谱系障碍（ASD）样行为的发展是必需的。然而，关于细菌感染的信息很少。在这项研究中，我们旨在阐明脂多糖（LPS）诱导的 MIA 模拟细菌感染对胎儿大脑发育的影响。我们证明 LPS 诱导的 MIA 促进了小鼠后代的 ASD 样行为。我们进一步发现，LPS 暴露诱导了急性期免疫反应：MIA 母亲的血清 IL-17A 水平升高，子宫中 Il17a mRNA 表达上调，产生 IL-17A 的 γδ T 细胞增加，胎儿大脑中 Il17ra mRNA 表达上调。阻断 LPS 诱导的 MIA 中的 IL-17A 可改善后代的 ASD 样行为。我们的数据表明，细菌诱导的母体 IL-17A 途径促进了后代的 ASD 样行为。
