Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, USA; Department of Psychiatry & Behavioral Health, The Ohio State University, Columbus, OH, USA; Biosciences Division, College of Dentistry, The Ohio State University, Columbus, OH, USA; Infectious Diseases Institute, The Ohio State University, Columbus, OH, USA; Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Infectious Diseases Institute, The Ohio State University, Columbus, OH, USA; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA.
Brain Behav Immun. 2021 Aug;96:28-39. doi: 10.1016/j.bbi.2021.05.004. Epub 2021 May 12.
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, T17 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.
母体在怀孕期间感染是后代精神健康障碍的已知风险因素。母体免疫激活 (MIA) 的动物模型提示了精神疾病的特定细胞和分子病因，但大多数模型依赖于病原体模拟物。在这里，我们开发了一种在怀孕期间感染活 H3N2 甲型流感病毒 (IAV) 的小鼠模型，该模型诱导强烈的炎症反应，但对母体和后代均无致命性。我们观察到 IAV 感染的母体出现典型的肺部炎症迹象和严重的体重增加减少。这伴随着胎盘内免疫细胞浸润和胎盘完整性部分破坏。然而，胎儿神经炎症的迹象不存在。模仿物诱导的 MIA 的其他特征，包括循环母性白细胞介素-17A 的增强，也不存在。呼吸道 IAV 感染确实导致转录因子 RORγt 在肠道表达上调，该因子是一组 T 淋巴细胞（T17 细胞）的主要调节因子，这些细胞大量参与 MIA 诱导的病因。尽管如此，随后的白细胞介素-17A 产生增加和伴随的明显肠道损伤并不明显。我们的结果表明，怀孕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在 MIA 研究中的重要性。
