Fungicidal activity of human neutrophils and monocytes on dermatophyte fungi, Trichophyton quinckeanum and Trichophyton rubrum.

Abstract

Human peripheral polymorphonuclear neutrophils exhibited potent cytotoxic activity against the dermatophyte fungi Tricophyton quinckeanum and T. rubrum as assessed by inhibition of fungal replication in Sabouraud's agar. Monocytes also showed cytotoxic activity, but this was less pronounced than that of neutrophils, while lymphocytes had no toxic effect. Cytotoxicity showed a linear relationship to the target cell:effector cell ratio, with significant killing detected at a ratio of one neutrophil to one fungal cell. Fungal killing was optimal at incubation times of 2-24 hr for T. rubrum and 2-48 hr for T. quinckeanum. Thereafter, neutrophils were unable to prevent fungal replication while remaining viable. cytotoxicity was markedly reduced by sodium azide, an agent that inhibits haem enzymes, and by catalase, but not by heat-inactivated catalase or superoxide dismutase. The fungicidal activity of neutrophils and monocytes was greatly increased by stimulation with phorbol myristate acetate (PMA) or with concanavalin A (Con A) compounds known to stimulate the secretion of lysosomal enzymes and the production of highly reactive oxygen intermediates. The cytotoxic activity of monocytes to T. quinckeanum, but not to T. rubrum, was also increased by Con A treatment. Neutrophil and monocyte phagocytosis of dermatophytes was demonstrated by electron microscopy studies. Disrupted T. quinckeanum and T. rubrum germlings were identified in the cytoplasm of the phagocytic cells, and similarly disruption of hyphae surrounded, but not engulfed, by neutrophils was also observed. These studies suggest that phagocytosis and/or oxidative products of the respiratory burst of neutrophils and monocytes may be implicated in the killing of dermatophytes in vivo.