The slow progression of Japanese encephalitis in aged mice is likely associated to B cell recruitment in the brain.

Abstract

The Japanese encephalitis virus (JEV) causes Japanese encephalitis (JE), a severe disease that primarily affects children and induces significant central nervous system complications. With the widespread adoption of vaccination in children, the incidence among older individuals has increased substantially. Despite this epidemiological shift, research on JEV infection in the elderly remains limited. We established JEV infection models using both aged and young mice to explore age-related differences in pathology and underlying mechanisms. Brain tissue samples were analyzed for pathological changes and viral tropism in major cell types. To further characterize immune response variations, we conducted transcriptomic sequencing on the brain tissues following JEV infection. Aged mice exhibited lower mortality, delayed disease progression, and milder brain pathology compared to young mice after JEV infection. Viral titers and infection rates of major brain cell types were similar in both groups. Transcriptomic analysis revealed diminished immune activation and weaker inflammatory responses in aged mice. Additionally, microglial activation and CD8⁺ T cell function were significantly reduced. Interestingly, JEV infection induced the selective recruitment of B cells in the brains of aged mice. These B cells may modulate the effects of CD8⁺ T cells in the disease process. Compared to young mice, aged mice showed enhanced resistance to JEV progression and reduced brain pathology. This resistance was associated with a weakened immune response in the aged brain, rather than differences in viral infection. The specific recruitment of B cells in the brains of aged mice may play a crucial role in limiting disease progression.