The intermediate filament GFAP is important for the control of experimental murine Staphylococcus aureus-induced brain abscess and Toxoplasma encephalitis.
The functional role of astrocytes exerted via their intermediate protein glial fibrillary acidic protein (GFAP) in CNS infections was studied in Staphylococcus aureus-induced brain abscess. Compared to wild type (WT) mice, GFAP(0/0) mice developed larger and more poorly demarcated inflammatory lesions paralleled by a significantly increased intracerebral bacterial load, a diffuse leukocytic infiltration of the contralateral hemisphere, purulent ventriculitis, vasculitis, and severe brain edema. These observations were correlated with the lack of a bordering function of activated astrocytes that strongly upregulated their GFAP expression in the abscess surrounding of WT mice. Clinically important, this lack of restriction of inflammation markedly aggravated the course of disease with manifestation of seizures and a severe weight loss in GFAP(0/0) mice. These data were paralleled by observations in the model of Toxoplasma encephalitis (TE) during which the intracerebral parasitic load was significantly increased. Moreover, tachyzoite-induced tissue necrosis was exclusively found in the brains of GFAP(0/0) mice in chronic TE. Collectively, these findings delineate a host defense function of astrocytes via restricting pathogenic spread and multiplication within the CNS, thereby contributing to the protection of the highly vulnerable brain parenchyma.
Stenzel
Werner
W
Abteilung für Neuropathologie, Universität zu Köln, Köln, Germany.
Soltek
Sabine
S
Schlüter
Dirk
D
Deckert
Martina
M
D000818:Animals; D001922:Brain Abscess / Q000235:genetics / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013203:Staphylococcal Infections / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000254:growth & development / Q000472:pathogenicity; D014122:Toxoplasma / Q000254:growth & development / Q000472:pathogenicity; D014124:Toxoplasmosis, Animal / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control
D005904:Glial Fibrillary Acidic Protein