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

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 IAVinfected 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 mimeticinduced MIA, including enhanced circulating maternal IL-17A, were also absent. Respiratory IAV infection did result in an upregulation in intestinal expression of transcription factor ROR gamma t, 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.

Automated summary

Research found that mild or moderately pathogenic IAV infection during pregnancy does not induce inflammation in the developing fetal brain, and did not observe the hallmarks of mimetic-induced MIA, highlighting the importance of using live pathogen infection models for MIA study.