Percorrer por autor "Hassan, Ahmed"
A mostrar 1 - 1 de 1
Resultados por página
Opções de ordenação
- Meningeal γδ T cells facilitate bacterial entry into the brain in neonatal meningitis and trigger long-term behavioural sequelaePublication . Lorga, Inês; Soares, Joana; Bravo, Joana; Mesquita, Pedro; Ribeiro, Nuno; Rodrigues, João; Hassan, Ahmed; Mesquita, Morgana; Cavadas, Bruno; Georgiev, Hristo; Magalhães, Ana; Summavielle, Teresa; Vilanova, Manuel; Ribot, Julie C.; Andrade, Elva Bonifácio; Bonifácio Andrade, Elva; Summavielle, TeresaNeonatal 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.