title: Tumor necrosis factor alpha enhances antifungal activities of polymorphonuclear and mononuclear phagocytes against Aspergillus fumigatus.
abstract: 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.
authors.affiliation: Third Department of Pediatrics, Hippokration Hospital, University of Thessaloniki, GR-54642, Salonika, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Roilides
authors.forename: A
authors.initials: A
authors.lastname: Dimitriadou-Georgiadou
authors.forename: T
authors.initials: T
authors.lastname: Sein
authors.forename: I
authors.initials: I
authors.lastname: Kadiltsoglou
authors.forename: T J
authors.initials: TJ
authors.lastname: Walsh
mesh_terms: D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016676:Macrophages, Alveolar / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects*; D011817:Rabbits; D016897:Respiratory Burst; D013172:Spores, Fungal / Q000276:immunology; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides