Mechanisms of Destruction of Aspergillus fumigatus Hyphae Mediated by Human Monocytes

Abstract

Normal monocytes attached to and destroyed Aspergillus hyphae by morphologic and metabolic criteria. Inhibition by anaerobiosis, azide, cyanide, halide-free conditions, catalase, histidine, and tryptophan suggested mediation of hyphal damage primarily through the myeloperoxidase system. However, myeloperoxidase-independent oxidative or nonoxidative mechanisms appeared active in hyphal damage by monocytes from patients with myeloperoxidase deficiency or chronic granulomatous disease (CGD). Moreover, hyphae were damaged by lysates and granule-enriched fractions of monocytes from patients with CGD, whereas comparable fractions of normal monocytes were active only with added halide and H2O2. Hyphal damage by both whole monocytes and granule-enriched fractions from patients with CGD was inhibited by polyanions, a result suggesting that cationic proteins may be involved. Hyphal damage by normal monocytes or monocytes from patients with CGD was inhibited by cells that lacked antihyphal activity (chlorpromazine-treated normal neutrophils or neutrophils from patients with CGD, respectively). This effect may predispose patients with CGD to chronic, invasive aspergillosis.