Moderately pathogenic maternal influenza A virus infection disrupts placental integrity but spares the fetal brain

Adrienne M. Antonson, Adam D. Kenney, Helen J. Chen, Kara N. Corps, Jacob S. Yount, Tamar L. Gur

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)28-39
Number of pages12
JournalBrain, Behavior, and Immunity
StatePublished - Aug 2021


  • Fetal development
  • Fetal neuroinflammation
  • Gestational infection
  • Infection during pregnancy
  • Influenza A virus
  • Influenza infection
  • Maternal immune activation
  • Maternal inflammation
  • Maternal viral infection
  • T helper 17 cells

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience


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