Citrobacter koseri brain abscess in the neonatal rat: survival and replication within human and rat macrophages

Autor: Hiroyuki Shimada, Harvey Pollack, Ignacio Gonzalez-Gomez, Stacy M. Townsend, Julie L. Badger
Rok vydání: 2003
Předmět:
Zdroj: Infection and immunity. 71(10)
ISSN: 0019-9567
Popis: A unique feature ofCitrobacter koseriis the extremely high propensity to initiate brain abscesses during neonatal meningitis. Previous clinical reports and studies on infant rats have documented manyCitrobacter-filled macrophages within the ventricles and brain abscesses. It has been hypothesized that intracellular survival and replication within macrophages may be a mechanism by whichC. koserisubverts the host response and elicits chronic infection, resulting in brain abscess formation. In this study, we showed thatC. kosericauses meningitis and brain abscesses in the neonatal rat model, and we utilized histology and magnetic resonance imaging technology to visualize brain abscess formation. Histology and electron microscopy (EM) revealed that macrophages (and not fibroblasts, astrocytes, oligodendrocytes, or neurons) were the primary target for long-termC. koseriinfection. To better understandC. koseripathogenesis, we have characterized the interactions ofC. koseriwith human macrophages. We found thatC. koserisurvives and replicates within macrophages in vitro and that uptake ofC. koseriincreases in the presence of human pooled serum in a dose-dependent manner. EM studies lend support to the hypothesis thatC. koseriuses morphologically different methods of uptake to enter macrophages. FcγRI blocking experiments show that this receptor primarily facilitates the entry of opsonizedC. koseriinto macrophages. Further, confocal fluorescence microscopy demonstrates thatC. koserisurvives phagolysosomal fusion and that more than 90% of intracellularC. koseriorganisms are colocalized within phagolysosomes. The ability ofC. koserito survive phagolysosome fusion and replicate within macrophages may contribute to the establishment of chronic central nervous system infection including brain abscesses.
Databáze: OpenAIRE