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Infection and Immunity, July 2000, p. 4225-4237, Vol. 68, No. 7
Department of Medicine, Division of
Infectious Diseases,1 and Departments of
Pathology2 and Microbiology and
Immunology,3 Albert Einstein College of
Medicine, Bronx, New York 10461
Received 31 January 2000/Returned for modification 17 March
2000/Accepted 19 March 2000
To produce chronic infection, microbial pathogens must escape host
immune defenses. Infection with the human pathogenic fungus Cryptococcus neoformans is typically chronic. To understand
the mechanism by which C. neoformans survives in tissue
after the infection of immunocompetent hosts, we systematically studied the course of pulmonary infection in mice by electron microscopy. The
macrophage was the primary phagocytic cell at all times of infection,
but neutrophils also ingested yeast. Alveolar macrophages rapidly
internalized yeast cells after intratracheal infection, and
intracellular yeast cells were noted at all times of infection from
2 h through 28 days. However, the proportion of yeast cells in the
intracellular and extracellular spaces varied with the time of
infection. Early in infection, yeast cells were found predominantly in
the intracellular compartment. A shift toward extracellular
predominance occurred by 24 h that was accompanied by macrophage
cytotoxicity and disruption. Later in infection, intracellular
persistence in vivo was associated with replication, residence in a
membrane-bound phagosome, polysaccharide accumulation inside cells, and
cytotoxicity to macrophages, despite phagolysosomal fusion. Many
phagocytic vacuoles with intracellular yeast had discontinuous
membranes. Macrophage infection resulted in cells with a distinctive
appearance characterized by large numbers of vacuoles filled with
polysaccharide antigen. Similar results were observed in vitro using a
macrophage-like cell line. Our results show that C. neoformans is a facultative intracellular pathogen in vivo.
Furthermore, our observations suggest that C. neoformans occupies a unique niche among the intracellular pathogens whereby survival in phagocytic cells is accompanied by intracellular
polysaccharide production.
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Cryptococcus neoformans Is a Facultative
Intracellular Pathogen in Murine Pulmonary Infection
*
Corresponding author. Mailing address: Albert Einstein
College of Medicine, Golding Building, Rm. 701, 1300 Morris Park Ave., Bronx, NY 10461. Phone: (718) 430-4259. Fax: (718) 430-8701. E-mail: feldmess{at}aecom.yu.edu.
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