Neuroimmune responses in the chicken brain during acute fowl adenovirus serotype 4 infection

Fowl adenovirus serotype 4 (FAdV-4) causes fatal hepatitis in chickens and has a substantial impact on the poultry industry. The virus primarily targets the liver in chickens. Although viral load in the brain has been previously reported, the association of acute FAdV-4 infection with brain immune response remains poorly characterized. Therefore, this study focuses on immune alterations in the brain during acute FAdV-4 infection.

Here, we investigated an increase in immune cell populations, along with the expression of barrier-related genes, to define the neuroimmune response during FAdV-4 infection.

Our results demonstrated that there was an alteration in the immune cell population, characterized by an increased frequencies of activated monocytes/macrophages and T cell subsets in the brain from infected chickens. Additionally, the CD44⁺CD8⁺ and γδ CD8⁺ were elevated among T cell subsets and accompanied by a surge in TNFA mRNA expression. The alteration was extended to the low expression of genes encoding tight-junction (TJ) proteins, such as TJP1, CLDN5, and OCLN, and a depletion in CLDN5 protein levels. This downregulation corresponded to the detection of FAdV-4 hexon DNA in the chicken brain homogenates from the infected group, suggesting a potential link between structural barrier alterations and viral presence.

Together, these findings suggest acute FAdV-4 infection-associated neuroimmune alterations, mapping a distinct immunophenotypic and transcriptional landscape within the avian brain.