Gres V, Lohrmann F, Fuchs V, Neuber J, Moghadam ZM, Lösslein AK, Bosch LFP, Figueiral-Martins T, Baasch S, Obwegs D, Monaco G, Henschel J, Knobeloch KP, Prinz M, Jung S, Kierdorf K, Sagar, Kolter J, Erny D, Henneke P.
Editor’s summary
Meningeal macrophages contribute to central nervous system (CNS) homeostasis and immune responses, but how infection shapes their development and function remains unclear. Using a mouse model of streptococcal meningoencephalitis, Gres et al. found that bacterial infection induced activation and loss of resident dural macrophages. During infection, macrophage replenishment shifted toward monocytes derived from monocyte–dendritic cell progenitors (MDPs), which had greater capacity to activate T cells. Bacterial infection also depleted myeloid progenitors from local reservoirs in the skull bone marrow, necessitating monocyte recruitment from peripheral sources. These findings demonstrate that bacterial meningoencephalitis reshapes monocyte recruitment and macrophage ontogeny in the CNS borders. —Claire Olingy
Abstract
Macrophages in the meninges contribute to immune defense of the central nervous system (CNS), yet their site-specific origin and function remain poorly understood. Using an intravenous model of streptococcal meningoencephalitis in mice, we found bacteria predominantly in the leptomeninges and dura. Nevertheless, monocyte infiltration into the leptomeninges and parenchyma strongly correlated with disease severity. In the dura, infection triggered activation and loss of resident macrophages, followed by rapid engraftment of inflammatory monocytes that transiently replenished the macrophage niche. Under homeostasis, dural monocytes were supplied CCR2 independently from adjacent skull bone marrow. During infection, this local source was insufficient, necessitating recruitment from peripheral bone marrow. Infection further reshaped monocyte ontogeny, increasing monocyte–dendritic cell progenitor–derived monocytes, which expressed higher major histocompatibility complex class II levels and persisted in the brain alongside CD4+ T cells during resolution. Together, these findings reveal dynamic, compartment-specific remodeling of monocyte recruitment and differentiation across CNS borders during bacterial meningoencephalitis.
