The histopathology of Candida albicans invasion in neonatal rat tissues and in the human blood-brain barrier in culture revealed by light, scanning, transmission and immunoelectron microscopy
A.S. Lossinsky1, A. Jong2, M. Fiala3, M. Mukhtar4, K.F. Buttle5 and M. Ingram6
1Immunohistochemistry and Electron Microscopy Laboratories, Neural Engineering Program, Huntington Medical Research Institutes, Pasadena, California, 2Department of Pediatrics, Children's Hospital of Los Angeles and the USC School of Medicine, Los Angeles, CA, 3Department of Medicine and Oral Biology, UCLA School of Medicine, Los Angeles, CA, 4Division of Infectious Diseases, Thomas Jefferson University School of Medicine, Philadelphia, PA, 5Resource for Visualization of Biological Complexities, Wadsworth Center, Albany, NY, and6Department of In Vitro Systems and Tissue Engineering, Huntington Medical Research Institutes, Pasadena, California
Offprint requests to: Dr. Albert S. Lossinsky, Neural Engineering Program, Laboratories of Immunohistochemistry and Electron Microscopy, Huntington Medical Research Institutes, 734 Fairmount Avenue, Pasadena, CA 91105. USA. e-mail: ALossinsky@aol.com
Summary. The present studies examined the effects of Candida albicans yeast and hyphal morphologies on tissue pathologies and transmigration properties of the fungus in two experimental models: 1) an in vivo, neonatal rat model, and 2) a cell culture model of human brain microvascular endothelial cells (ECs) (BMVEC). We inoculated a hyphae-producing strain (CAI4-URA3) and a non-hyphae-producing strain (CAI4) of C. albicans into 4-10 day old rats and BMVEC cultures. Animals were inoculated by intraperitonal (i.p.), intranasal (i.n.), oral (p.o.) and intracerebral (i.c.) routes and several tissues were examined after 24-48 hrs. Rats inoculated i.p. with the hyphae-producing strain showed pathology in the kidneys, liver, spleen, and other tissues associated with inoculation tracks of the nose, and muscle and connective tissues of the abdominal wall. Few animals inoculated i.p., however, presented evidence of meningitis. The non-hyphae phase yeast produced neither tissue pathology nor meningitis. Animals inoculated i.c. with the hyphae strain after 1 and 3 hrs expressed minimal meningitis, with an increasing neutrophillic meningitis between 4 and 18 hrs after inoculation. At 18 hrs after i.c. inoculation, however, the inflammatory foci and brain pathology were extensive and demonstrated mycelia within the lateral ventricles associated with necrosis of adjacent brain tissue. Neutrophillic meningitis at this time period was pronounced. BMVEC co-cultured 1-2 hrs with both C. albicans strains showed EC phagocytosis of hyphae and blastospores into intercellular adhesion molecule-1 (ICAM-1)-labeled caveolae suggesting a transcellular role for ICAM-1 in the internalization process of C. albicans. Histol Histopathol 21, 1029-1041 (2006)
Key words: Candida albicans, Blood-brain barrier
DOI: 10.14670/HH-21.1029