Work

FOXO1a and IL10/IL10rb-associated responses coordinate myelin preservation and immune–redox homeostasis during viral neuroinflammation

Year: 2026

Type: article

Abstract: Neurotropic viral infections can cause rapid neurological deterioration, but disease severity reflects pathogen burden and the capacity of neural tissues to tolerate infection-associated stress. Using a zebrafish larval model of nervous necrosis virus (NNV) infection, we found that early infection induced myelin abnormalities, inflammatory activation, redox and iron dyshomeostasis, and reduced expression of oligodendrocyte-lineage and myelin-associated markers. Genetic ablation of foxo1a or il10rb increased viral burden and exacerbated inflammatory, oxidative, ferroptosis-associated, and myelin-related abnormalities, whereas genetic rescue partially restored these phenotypes. FOXO1a increased il10 promoter-reporter activity in a heterologous system, and il10 supplementation partially restored socs3 , mbp , and gpx4 expression while reducing tnfα expression in foxo1a-deficient larvae. In contrast, il10 supplementation failed to restore the expression of above three marker genes in il10rb-deficient larvae. Pharmacological modulation of FOXO-related stress responses or lipid peroxidation during infection partially preserved myelin ultrastructure, improved larval survival, and reduced viral readouts. Collectively, these findings support a coordinated FOXO1a- and IL10/IL10rb-associated protective network, though it may not operate through a strictly linear signaling cascade, that actively maintains immune-redox homeostasis and myelin preservation during acute NNV infection. These results further suggest that prioritizing anti-inflammatory pathway activation to sustain immune equilibrium, rather than solely targeting viral clearance, could represent a more effective therapeutic strategy for mitigating neurotropic viral pathogenesis.

Source: Journal of Neuroinflammation

DOI: 10.1186/s12974-026-04029-1