2025-09-24 イリノイ大学アーバナ・シャンペーン校
<関連情報>
- https://aces.illinois.edu/news/pregnant-mice-severe-flu-harmful-molecules-can-breach-fetal-barriers
- https://www.sciencedirect.com/science/article/pii/S0889159125003034
妊娠中のインフルエンザAウイルス感染は、母体血液由来分子の胎児組織への移行を増加させる Influenza A virus infection during pregnancy increases transfer of maternal bloodborne molecules to fetal tissues
Rafael J. Gonzalez-Ricon, Ashley M. Otero, Izan Chalen, Jeffrey N. Savas, Shakirat Adetunji, Adrienne M. Antonson
Brain, Behavior, and Immunity Available online: 6 August 2025
DOI:https://doi.org/10.1016/j.bbi.2025.106069
Highlights
- Maternal influenza infection increases fetal exposure to maternally derived tracers.
- Fetal blood brain barrier dysfunction is evident in the SVZ and ChP.
- Fibrinogen accumulation in the SVZ and ChP correlates with Iba1 intensity.
- Increased vascular permeability may contribute to altered fetal brain development.
Abstract
Influenza A virus (IAV) infection during pregnancy is linked to heightened risk for neurodevelopmental disorders (NDDs) in the offspring. The precise pathophysiological mechanism(s) underling this association remains an active topic of research. We propose that maternal immune activation (MIA) triggered by IAV infection can disrupt selective permeability at the maternal-fetal interface, leading to increased transfer of blood-derived molecules into the fetal compartment. Some of these molecules might be responsible for the initiation of inflammatory cascades implicated in NDD etiology. Using a murine model of seasonal IAV infection during pregnancy, we examined placental and fetal brain barrier properties following maternal IAV challenge. Our findings demonstrate an enhanced transplacental transfer of fluorescently labeled tracers from maternal circulation to key neurodevelopmental regions, including the subventricular zone (SVZ) and choroid plexus (ChP) of fetal brains. This effect was most pronounced in fetuses from dams exposed to the highest dose of IAV. Notably, a similar pattern was observed for accumulation of the bloodborne neuroinflammatory molecule fibrinogen in these same brain regions, which was further amplified in response to the highest IAV dose. Moreover, fibrinogen accumulation was positively correlated with Iba1+ cell immunofluorescence, suggesting a potential interaction between fibrinogen and Iba1+ cells. Collectively, these findings suggest that IAV-induced MIA enhances transplacental transfer of blood-derived molecules into fetal tissues, potentially activating proinflammatory pathways in Iba1+ cells.
