06/02-2023 - Rejane RUA : When brain borders take center stage: role of meningeal macrophages in neuroinflammation and neurodevelopment

LES LUNDIS DE SAINT-ANTOINE

Bâtiment Kourilsky - 13h–14h

Salle des Conférences (Rez de Chaussée),

184 rue du Faubourg Saint-Antoine, Paris

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LUNDI 06 FEVRIER 2023

When brain borders take center stage: role of meningeal macrophages in neuroinflammation and neurodevelopment

Rejane RUA

CRCN- Centre d’Immunologie de Marseille-Luminy

invitée par Equipe de Guillaume Dorothée (Equipe DOROTHEE (guillaume.dorothée@inserm.fr))

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Due to the vital importance of the Central Nervous System (CNS), its infection and inflammation have to be tightly controlled. The surface of the CNS is connected to the periphery by a rich and complex tissue, the meninges. They contain a vast network of macrophages endowed with elusive functions. We mainly focus on three functional axes. First, at steady state, we found that meningeal macrophages nurture the skull and the brain during the perinatal stage, and their absence leads to defects in both the calvaria development and in neurogenesis. Second, we show that meningeal macrophage inflammation in the perinatal stage can be detrimental and correlates with neurodevelopmental disorders and abnormal behavior in mice. Lastly, in adult mice, we find that meningeal macrophage can be protective in the context of fatal neuroinfection: using innovative depletion strategies in experimental mouse models, we discovered that meningeal macrophage populations represent the first line of protection against a neuroinvasive pathogen (LCMV). In their absence, specific areas in the meninges become highly infected, leading to fatal brain disease. Thus, meningeal macrophages seem to be important guardians of CNS integrity at both perinatal and adult stages, and alteration of their activation status can lead to neurodevelopmental and neuroinflammatory issues.

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