title: Inteferon gamma and granulocyte-macrophage colony-stimulating factor augment the antifungal activity of human polymorphonuclear leukocytes against Scedosporium spp.: comparison with Aspergillus spp.
abstract: While Aspergillus spp. have been the most frequent filamentous fungi causing infections in immunocompromised patients, Scedosporium spp. are emerging as life-threatening pathogens. We studied the effects of interferon gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) alone or combined on the antifungal activities of human polymorphonuclear leukocytes (PMN) against Scedosporium apiospermum and Scedosporium prolificans. We paralleled these activities to those against Aspergillus fumigatus and Aspergillus flavus. Incubation of PMN with IFN-gamma and GM-CSF for 22 h enhanced PMN-induced hyphal damage of both Aspergillus spp. and S. prolificans (p < 0.05) but not of S. apiospermum. However, hyphae of S. apiospermum were damaged significantly more after incubation with PMN that had been treated with IFN-gamma and GM-CSF for 2 h. In addition, incubation of PMN with GM-CSF for 2 h enhanced PMN oxidative burst measured as superoxide anion (O2-) production in response to nonopsonized hyphae of A. flavus and Scedosporium spp. (p < 0.05). In contrast, after 2 h, IFN-gamma and GM-CSF alone did not enhance PMN O2- in response to opsonized hyphae of A. flavus and Scedosporium spp.; however, the combination of IFN-gamma and GM-CSF showed significant enhancement against these species. Thus, IFN-gamma and GM-CSF, particularly in combination, demonstrate a species- and time-dependent augmentation of PMN responses to Scedosporium spp.
authors: Third Department of Pediatrics, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece.
authors: Cristina
authors: C
authors: Gil-Lamaignere
authors: Richard M
authors: RM
authors: Winn
authors: Maria
authors: M
authors: Simitsopoulou
authors: Avgi
authors: A
authors: Maloukou
authors: Thomas J
authors: TJ
authors: Walsh
authors: Emmanuel
authors: E
authors: Roilides
mesh_terms: D001231:Aspergillus flavus / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D025301:Hyphae / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D021681:Scedosporium / Q000276:immunology*; D013045:Species Specificity; D013997:Time Factors
chemical_list: D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor