Cryptococcus neoformans is a facultative intracellular pathogen in murine pulmonary infection

Citation
M. Feldmesser et al., Cryptococcus neoformans is a facultative intracellular pathogen in murine pulmonary infection, INFEC IMMUN, 68(7), 2000, pp. 4225-4237
Citations number
62
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
INFECTION AND IMMUNITY
ISSN journal
0019-9567 → ACNP
Volume
68
Issue
7
Year of publication
2000
Pages
4225 - 4237
Database
ISI
SICI code
0019-9567(200007)68:7<4225:CNIAFI>2.0.ZU;2-9
Abstract
To produce chronic infection, microbial pathogens must escape host immune d efenses. Infection with the human pathogenic fungus Cryptococcus neoformans is typically chronic. To understand the mechanism by which C. neoformans s urvives in tissue after the infection of immunocompetent hosts, we systemat ically studied the course of pulmonary infection in mice by electron micros copy, The macrophage was the primary phagocytic cell at all times of infect ion, but neutrophils also ingested yeast. Alveolar macrophages rapidly inte rnalized yeast cells after intratracheal infection, and intracellular yeast cells were noted at ail times of infection from 2 h through 28 days. Howev er, the proportion of yeast cells in the intracellular and extracellular sp aces varied with the time of infection. Early in infection, yeast cells wer e found predominantly in the intracellular compartment. A shift toward extr acellular 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 phag osome, polysaccharide accumulation inside cells, and cytotoxicity to macrop hages, despite phagolysosomal fusion. Many phagocytic vacuoles with intrace llular yeast had discontinuous membranes. Macrophage infection resulted in cells with a distinctive appearance characterized by large numbers of vacuo les filled with polysaccharide antigen. Similar results were observed in vi tro using a macrophage-like cell line. Our results show that C. neoformans is a facultative intracellular pathogen in vivo. Furthermore, our observati ons suggest that C. neoformans occupies a unique niche among the intracellu lar pathogens whereby survival in phagocytic cells is accompanied by intrac ellular polysaccharide production.