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Analysis of Microglia and Monocyte-derived Macrophages from the Central Nervous System by Flow Cytometry
Published on: June 22, 2017
Bacterial infection reshapes monocyte and macrophage ontogeny at the CNS borders
Vitka Gres1, Florens Lohrmann1,2, Vidmantė Fuchs3,4
1Institute for Infection Prevention and Control, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany.
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.
Insights
This study reveals how monocytes infiltrate the brain during meningitis, replacing resident macrophages in the dura and differentiating into specialized cells that aid in immune defense and recovery. Understanding these processes is key to developing new treatments for CNS infections.
Area of Science:
- Neuroimmunology
- Infectious Diseases
- Cellular Biology
Background:
- Macrophages in the meninges are crucial for central nervous system (CNS) immune defense.
- Their specific origins and functions during CNS infections are not well understood.
Purpose of the Study:
- To investigate the origin and function of meningeal macrophages during experimental streptococcal meningoencephalitis in mice.
- To elucidate the dynamic changes in monocyte recruitment and differentiation across CNS borders during infection.
Main Methods:
- Intravenous model of streptococcal meningoencephalitis in mice.
- Analysis of bacterial distribution, monocyte infiltration, and macrophage populations in the leptomeninges, dura, and parenchyma.
- Tracking of monocyte origins and differentiation pathways.
Main Results:
- Bacteria were predominantly found in the leptomeninges and dura, while monocyte infiltration correlated with disease severity.
- Infection led to activation and loss of resident dural macrophages, replaced by inflammatory monocytes.
- Dural monocytes shifted from a CCR2-independent source to peripheral bone marrow recruitment during infection.
- Monocyte differentiation was altered, increasing monocyte-dendritic cell progenitor-derived monocytes with enhanced MHC class II expression.
Conclusions:
- Monocyte recruitment and differentiation are dynamically remodeled across CNS borders during bacterial meningoencephalitis.
- These findings highlight compartment-specific responses within the meninges and CNS parenchyma.
- Understanding these cellular dynamics is crucial for developing targeted therapies for CNS infections.
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