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Moderately pathogenic maternal influenza A virus infection disrupts placental integrity but spares the fetal brain
Brain, Behavior, and Immunity ( IF 8.8 ) Pub Date : 2021-05-12 , DOI: 10.1016/j.bbi.2021.05.004
Adrienne M Antonson 1 , Adam D Kenney 2 , Helen J Chen 3 , Kara N Corps 4 , Jacob S Yount 2 , Tamar L Gur 5
Affiliation  

Maternal infection during pregnancy is a known risk factor for offspring mental health disorders. Animal models of maternal immune activation (MIA) have implicated specific cellular and molecular etiologies of psychiatric illness, but most rely on pathogen mimetics. Here, we developed a mouse model of live H3N2 influenza A virus (IAV) infection during pregnancy that induces a robust inflammatory response but is sublethal to both dams and offspring. We observed classic indicators of lung inflammation and severely diminished weight gain in IAV-infected dams. This was accompanied by immune cell infiltration in the placenta and partial breakdown of placental integrity. However, indications of fetal neuroinflammation were absent. Further hallmarks of mimetic-induced MIA, including enhanced circulating maternal IL-17A, were also absent. Respiratory IAV infection did result in an upregulation in intestinal expression of transcription factor RORγt, master regulator of a subset of T lymphocytes, TH17 cells, which are heavily implicated in MIA-induced etiologies. Nonetheless, subsequent augmentation in IL-17A production and concomitant overt intestinal injury was not evident. Our results suggest that mild or moderately pathogenic IAV infection during pregnancy does not inflame the developing fetal brain, and highlight the importance of live pathogen infection models for the study of MIA.



中文翻译:


中度致病性母体甲型流感病毒感染会破坏胎盘完整性,但不会影响胎儿大脑



怀孕期间母亲感染是后代心理健康障碍的已知危险因素。母体免疫激活(MIA)的动物模型暗示了精神疾病的特定细胞和分子病因,但大多数依赖于病原体模拟物。在这里,我们开发了一种怀孕期间活 H3N2 甲型流感病毒 (IAV) 感染的小鼠模型,该模型会诱导强烈的炎症反应,但对母鼠和后代都是亚致死的。我们观察到感染 IAV 的母鼠肺部炎症的典型指标和体重增加严重减少。伴随着胎盘中的免疫细胞浸润和胎盘完整性的部分破坏。然而,没有胎儿神经炎症的迹象。模拟诱导的 MIA 的其他特征,包括母体 IL-17A 循环增强,也没有出现。呼吸道 IAV 感染确实导致肠道转录因子 RORγt 表达上调,RORγt 是 T 淋巴细胞亚群( TH 17 细胞)的主要调节因子,与 MIA 诱导的病因密切相关。尽管如此,随后 IL-17A 产生的增加和伴随的明显肠道损伤并不明显。我们的研究结果表明,妊娠期间轻度或中度致病性 IAV 感染不会使发育中的胎儿大脑发炎,并强调了活病原体感染模型对于 MIA 研究的重要性。

更新日期:2021-07-20
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