Circulating monocytes engraft in the brain, differentiate into microglia and contribute to the pathology following meningitis in mice.
Previous studies have demonstrated a potential role of brain endogenous microglia and meningeal macrophages in inflammation and brain injury during bacterial meningitis. However, the contribution of previously engrafted monocytes and microglia to this process is still unknown. We therefore used genetically labelled bone marrow-derived cells from transgenic mice expressing the green fluorescent protein (GFP) under the chicken beta-actin promoter to deliver fluorescently labelled monocytes to the diseased brain. Approximately 24 hours after Streptococcus pneumoniae infection, GFP-expressing parenchymal microglia changed their morphology to an activated phenotype and upregulated major histocompatibility complex class II molecules. Bacterial meningitis increased the engraftment of GFP+ monocytes and their differentiation to microglia during the post-inflammatory period, but not during acute meningitis. Importantly, these newly recruited monocytes became an integral part of the pool of parenchymal microglia and contributed to the clearance of damaged tissue by increased lysosomal activity and close location to apoptotic cells. Thus, circulating cells entering the brain such as monocytes/macrophages might provide a potential cellular target for the treatment of the tissue damage following meningitis via peripheral cell therapy.
Djukic
Marija
M
Department of Neurology, Georg August University, Göttingen, Germany.
Mildner
Alexander
A
Schmidt
Hauke
H
Czesnik
Dirk
D
Brück
Wolfgang
W
Priller
Josef
J
Nau
Roland
R
Prinz
Marco
M
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods; D001921:Brain / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology*; D002531:Cerebellum / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000032:analysis; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D049408:Luminescent Agents / Q000032:analysis; D008264:Macrophages / Q000473:pathology; D008586:Meningitis, Pneumococcal / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000473:pathology*; D009000:Monocytes / Q000473:pathology*; D013702:Temporal Lobe / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology
D000949:Histocompatibility Antigens Class II; D049408:Luminescent Agents; D049452:Green Fluorescent Proteins