Meningeal γδ T cells facilitate bacterial entry into the brain in neonatal meningitis and trigger long-term behavioural sequelae

Neonatal bacterial meningitis is a life-threatening condition and a leading cause of neurodevelopmental impairment among survivors. Despite its prevalence, the role of meningeal immunity on disease pathology during early life remains largely unexplored. Using a clinically relevant mouse model of neonatal group B streptococcal meningitis and single-cell RNA sequencing, we observed that IL-17A (IL-17)-producing γδ T cells (γδ17 T cells) accumulate in the meninges during the acute phase of infection and persist throughout the lifespan. Importantly, mice deficient in γδ T cells or in IL-17 show a significantly lower bacterial colonisation in the brain parenchyma, and IL-17 neutralisation in the cerebrospinal fluid leads to a similar phenotype. Reduced blood-brain barrier permeability in the absence of γδ T cells results in decreased bacterial invasion and diminished microglia activation. Wild-type but not γδ T cell-deficient mice surviving infection exhibit increased hyperactivity and open space anxiety during early adulthood, a behavioural profile that may reflect attention deficit and hyperactivity (ADHD)-like tendencies. Altogether, these findings establish a pathogenic role for meningeal γδ17 T cells in early life, uncovering a key mechanism that drives long-term sequelae in GBS neonatal meningitis.

Palavras-chave

Group B Streptococcus Meninges Neonatal meningitis γδ T cells IL-17 ADHD

URI

http://hdl.handle.net/10400.22/32525

Citação

Lorga, I., Soares, J., Bravo, J., Mesquita, P., Ribeiro, N., Rodrigues, J., Hassan, A., Mesquita, M., Cavadas, B., Georgiev, H., Magalhães, A., Summavielle, T., Vilanova, M., Ribot, J. C., & Andrade, E. B. (2025). Meningeal γδ T cells facilitate bacterial entry into the brain in neonatal meningitis and trigger long-term behavioural sequelae (p. 2025.11.07.686929). bioRxiv. https://doi.org/10.1101/2025.11.07.686929

DOI

10.1101/2025.11.07.686929

Coleções

ESS - APCT - Artigos
ESS - CF - Artigos

Licença CC

Sem licença CC

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