Tumor necrosis factor alpha enhances antifungal activities of polymorphonuclear and mononuclear phagocytes against Aspergillus fumigatus

• Published in: Infection and immunity 1998-12, Vol.66 (12), p.5999-6003
• Main Authors: ROILIDES, E, DIMITRIADOU-GEORGIADOU, A, SEIN, T, KADILTSOGLOU, I, WALSH, T. J
• Format: Article
• Language: English
• Subjects: Animals; Aspergillus fumigatus; Aspergillus fumigatus - immunology; Biological and medical sciences; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Fungal and Parasitic Infections; Humans; Macrophages, Alveolar - immunology; Microbiology; Monocytes - immunology; Mycology; Neutrophils - immunology; Pathogenicity, host-agent relations, miscellaneous strains, epidemiology; Phagocytosis - drug effects; Rabbits; Respiratory Burst; Spores, Fungal - immunology; Superoxides - metabolism; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/iai.66.12.5999-6003.1998

Invasive aspergillosis is a serious complication in immunocompromised patients. The effects of recombinant human tumor necrosis factor alpha (TNF-alpha) on antifungal activities of human neutrophils (polymorphonuclear leukocytes [PMNs]), human monocytes (MNCs), and rabbit pulmonary alveolar macrophages (PAMs) against Aspergillus fumigatus were studied. The percentage of PMN-induced hyphal damage was increased after 30 min of incubation of PMNs with 0.1 ng of TNF-alpha per ml at 37 degreesC (P = 0.043). At 0.1 to 10 ng/ml, TNF-alpha also increased superoxide anion (O2-) produced by PMNs in response to phorbol myristate acetate, N-formylmethionyl leucyl phenylalanine, and unopsonized hyphae (P < 0.01) but did not exert any effect on PMN phagocytosis of conidia in the presence of serum. By comparison, TNF-alpha induced only a slight increase in O2- production by MNCs in response to phorbol myristate acetate (P = 0.05) and no concomitant increase in the percentage of MNC-induced hyphal damage. Incubation of MNCs with TNF-alpha at 0.001 to 10 ng/ml for 2 days had no effect on phagocytosis or conidiocidal activity. By contrast, incubation of PAMs with TNF-alpha at 0.1 to 10 ng/ml for 2 days increased phagocytosis of conidia (P = 0.03). Thus, TNF-alpha augments the capacity of PMNs to damage Aspergillus hyphae, possibly through enhanced oxidative mechanisms, and increases PAM phagocytic activity against conidia. As such, TNF-alpha may have an important role in host defense against aspergillosis, and neutralization of its activity may be complicated by increased susceptibility to aspergillosis.