2025-06-18 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/study-links-influenza-viral-infection-microbiome-brain-gene-expression-changes
- https://news.illinois.edu/study-links-influenza-a-viral-infection-to-microbiome-brain-gene-expression-changes/?utm_source=email+&utm_medium=email
- https://www.sciencedirect.com/science/article/pii/S0378113525001798
- https://karger.com/dne/article-abstract/40/2/104/107641/Altered-Hippocampal-Gene-Expression-and-Morphology
母豚のワクチン接種は、A型インフルエンザウイルスに関連したマイクロバイオームと海馬遺伝子発現の変化から子豚を部分的に保護する Maternal vaccination partially protects piglets against influenza A virus associated alteration of the microbiome and hippocampal gene expression
Christopher A. Gaulke, Fangfeng Yuan, Lufan Yang, Luoyan Duan, Meghan G. Connolly, Shih-Hsuan Hsiao, Adrienne M. Antonson, Ying Fang
Veterinary Microbiology Available online: 7 May 2025
DOI:https://doi.org/10.1016/j.vetmic.2025.110544
Highlights
- Influenza A (IAV) infection alters nasal and gut microbiome in newborn piglets.
- IAV infection disrupts expression of genes involved in neurological development.
- Altered brain gene expression during IAV infection links with changes in microbiome.
- Maternal vaccination partially protects against microbiome and neurological effects.
Abstract
Influenza A virus (IAV) causes respiratory disease with systemic complications in a variety of avian and mammalian hosts, including humans and pigs. Infection with IAV in newborns can be particularly damaging as viral infection is known to disrupt the rapid developmental processes that occur during this period. Maternal IAV vaccination can reduce the risk of IAV infection in infants, but it is unknown whether passive transfer of anti-IAV antibodies protect against the downstream complications of infection. In this study, we evaluated the impact of maternal vaccination on the gut and nasal microbiota development and hippocampal transcriptome in neonatal piglets infected with influenza A virus. Sows were either vaccinated with an experimental influenza A vaccine at 70- and 90-days gestation, or mock-vaccinated with PBS. Neonatal piglets born from vaccinated and unvaccinated sows were challenged with a pathogenic IAV isolate or mock-challenged with PBS at 6 days post-farrowing and euthanized five days post challenge. Vaccination significantly reduced lung lesions and infectious viral load in piglets. Nasal and gut microbial community development was also partially protected from viral disruption as indicated by increased deviation from pre-challenge timepoints compared to animals challenged with the virus from unvaccinated mothers. Bulk RNA sequencing of hippocampal tissue identified 1146 differentially expressed genes (FDR < 0.05) between groups. IAV-infected piglets from vaccinated sows showed increases in genes related to viral immune responses, while IAV-infected piglets from unvaccinated sows showed increases in genes related to neurogenesis and decreases in genes related to vascular development. Many of these differentially regulated genes were strongly correlated with microbial community abundances, indicating that the microbiota may contribute to IAV outcomes. Notably, nasal microbial abundances intricately connected with hippocampal gene expression patterns, suggesting a strong nasal microbiome-brain communication axis in early development. Together, our results indicate that maternal vaccination partially protects neonatal piglets against influenza virus infection and mitigates the potential long-term impacts of IAV infection on the microbiome and cognition.
母体呼吸器ウイルス感染後の胎児子豚における海馬遺伝子発現と形態の変化 Altered Hippocampal Gene Expression and Morphology in Fetal Piglets following Maternal Respiratory Viral Infection
Adrienne M. Antonson;Bindu Balakrishnan;Emily C. Radlowski;Geraldine Petr;Rodney W. Johnson
Developmental Neuroscience Published:June 21 2018
DOI:https://doi.org/10.1159/000486850
Abstract
Maternal infection during pregnancy increases the risk of neurobehavioral problems in offspring. Evidence from rodent models indicates that the maternal immune response to infection can alter fetal brain development, particularly in the hippocampus. However, information on the effects of maternal viral infection on fetal brain development in gyrencephalic species is limited. Thus, the objective of this study was to assess several effects of maternal viral infection in the last one-third of gestation on hippocampal gene expression and development in fetal piglets. Pregnant gilts were inoculated with porcine reproductive and respiratory syndrome virus (PRRSV) at gestational day (GD) 76 and the fetuses were removed by cesarean section at GD 111 (3 days before anticipated parturition). The gilts infected with PRRSV had elevated plasma interleukin-6 levels and developed transient febrile and anorectic responses lasting approximately 21 days. Despite having a similar overall body weight, fetuses from the PRRSV-infected gilts had a decreased brain weight and altered hippocampal gene expression compared to fetuses from control gilts. Notably, maternal infection caused a reduction in estimated neuronal numbers in the fetal dentate gyrus and subiculum. The number of proliferative Ki-67+ cells was not altered, but the relative integrated density of GFAP+ staining was increased, in addition to an increase in GFAP gene expression, indicating astrocyte-specific gliosis. Maternal viral infection caused an increase in fetal hippocampal gene expression of the inflammatory cytokines TNF-α and IFN-γ and the myelination marker myelin basic protein. MHCII protein, a classic monocyte activation marker, was reduced in microglia, while expression of the MHCII gene was decreased in hippocampal tissue of the fetuses from PRRSV-infected gilts. Together, these data suggest that maternal viral infection at the beginning of the last trimester results in a reduction in fetal hippocampal neurons that is evident 5 weeks after infection, when fetal piglets are near full term. The neuronal reduction was not accompanied by pronounced neuroinflammation at GD 111, indicating that any activation of classic neuroinflammatory pathways by maternal viral infection, if present, is mostly resolved by parturition.
