Macrophage-dependent candidacidal mechanisms in the murine system. Comparison of murine Kupffer cell and peritoneal macrophage candidacidal mechanisms.
Candida albicans infection is common in immunocompromised patients. The role of fixed tissue macrophages (M phi), including Kupffer cells (KC) and peritoneal macrophages (PM phi), in host defense against C. albicans is unclear. This study examined murine M phi candidacidal mechanisms and evaluated the in vitro role of the macrophage-activating factor IFN-gamma in augmenting these mechanisms. The effect of in vivo administration of IFN-gamma on survival after lethal C. albicans challenge in the murine system was also assessed. Percent PM phi and KC ingestion of C. albicans were similar. Prior opsonization of Candida increased the percentage of M phi ingestion of this pathogen. PM phi and KC phagocytic function was similar for both nonopsonized and opsonized C. albicans, but KC demonstrated markedly decreased ability to kill this pathogen (O2-, Candida killing). IFN-gamma enhanced KC and PM phi candidacidal activity. PM phi and KC Ag presentation was increased in early Candida infection, but diminished in established infection, when the majority of animals died. C. albicans failed to elicit significant amounts of either IL-1 or TNF compared with LPS stimulation of PM phi and KC in vitro. IFN-gamma treatment in vivo was associated with significantly improved survival (p < 0.01).
Redmond
H P
HP
Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia 19104.
Shou
J
J
Gallagher
H J
HJ
Kelly
C J
CJ
Daly
J M
JM
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology; D007728:Kupffer Cells / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D010529:Peritoneal Cavity / Q000166:cytology; D010587:Phagocytosis; D016897:Respiratory Burst; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D007371:Interferon-gamma