Tumor necrosis factor and Candida albicans.
Analysis of defense mechanisms against C. albicans, which causes opportunistic infections in immunocompromised hosts, indicates that a complex interaction of human large granular lymphocytes (LGL) that exhibit natural killer activity and neutrophils via cytokines takes place to control fungal growth, LGL respond rapidly upon exposure to C. albicans by releasing cytokines, such as tumor necrosis factor (TNF), which then act immediately upon polymorphonuclear neutrophils (PMN) to stimulate their antifungal activity. We also found that C. albicans can induce TNF from PMN. TNF was measured by a 18 h 51Cr release assay using the highly-sensitive WEHI 164 tumor cells. Exposure of PMN to C. albicans for 3 h was sufficient to detect TNF release and peak induction was observed at 8-18 h. This release was inhibitable by Actinomycin D, an inhibitor of RNA synthesis, as well as by emetine and cycloheximide, which block protein synthesis. The TNF from PMN was characterized by neutralization with a specific monoclonal antibody against human TNF. To assess the role of TNF in PMN function, recombinant TNF was added to PMN with C. albicans in a highly-sensitive 3H-glucose incorporation assay to measure antifungal activity in PMN. Less than 1 unit/ml of TNF was able to significantly enhance PMN activity against C. albicans. These results represent a new finding that TNF production is a normal response of PMN to stimulation by fungi and suggest that release of TNF may be related to autocrine activation of PMN effector function to control fungal growth.
Djeu
J Y
JY
University of South Florida College of Medicine, Department of Medical Microbiology and Immunology, Tampa 33612.
D002176:Candida albicans / Q000254:growth & development / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha