title: MRI confirms loss of blood-brain barrier integrity in a mouse model of disseminated candidiasis.
abstract: Disseminated candidiasis primarily targets the kidneys and brain in mice and humans. Damage to these critical organs leads to the high mortality associated with such infections, and invasion across the blood-brain barrier can result in fungal meningoencephalitis. Candida albicans can penetrate a brain endothelial cell barrier in vitro through transcellular migration, but this mechanism has not been confirmed in vivo. MRI using the extracellular vascular contrast agent gadolinium diethylenetriaminepentaacetic acid demonstrated that integrity of the blood-brain barrier is lost during C. albicans invasion. Intravital two-photon laser scanning microscopy was used to provide the first real-time demonstration of C. albicans colonizing the living brain, where both yeast and filamentous forms of the pathogen were found. Furthermore, we adapted a previously described method utilizing MRI to monitor inflammatory cell recruitment into infected tissues in mice. Macrophages and other phagocytes were visualized in kidney and brain by the administration of ultrasmall iron oxide particles. In addition to obtaining new insights into the passage of C. albicans across the brain microvasculature, these imaging methods provide useful tools to study further the pathogenesis of C. albicans infections, to define the roles of Candida virulence genes in kidney versus brain infection and to assess new therapeutic measures for drug development.
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1500, USA.
authors.forename: Dhammika H M L P
authors.initials: DH
authors.lastname: Navarathna
authors.forename: Jeeva
authors.initials: J
authors.lastname: Munasinghe
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Lizak
authors.forename: Debasis
authors.initials: D
authors.lastname: Nayak
authors.forename: Dorian B
authors.initials: DB
authors.lastname: McGavern
authors.forename: David D
authors.initials: DD
authors.lastname: Roberts
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000382:microbiology* / Q000473:pathology*; D002176:Candida albicans / Q000254:growth & development / Q000502:physiology*; D002177:Candidiasis / Q000382:microbiology / Q000473:pathology*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D019786:Gadolinium DTPA / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging; D008578:Meninges / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010586:Phagocytes / Q000473:pathology; D015203:Reproducibility of Results; D013113:Spin Labels
chemical_list: D013113:Spin Labels; D019786:Gadolinium DTPA
keywords: Candida albicans; MRI; blood-brain barrier; extracellular vascular contrast agent Gd-DTPA; intravital two-photon microscopy; murine disseminated candidiasis; ultrasmall iron oxide particles