title: Transient overexpression of gamma interferon promotes Aspergillus clearance in invasive pulmonary aspergillosis.
abstract: Cytokines are critical molecules necessary for normal lung pathogen host defences. Gamma interferon (IFN-gamma) and T1-phenotype immune responses are important components of host defence against Aspergillus. Therefore, we hypothesized that transient overexpression of IFN-gamma within the lung could augment host immunity against Aspergillus. Here it was showed that intranasal administration of 5 x 10(7) colony-forming units (CFU) of Aspergillus fumigatus (Af ) induced the expression of IFN-gamma. Mice were intranasally (i.n) administrated with 5 x 10(8) PFU of a recombinant adenovirus vector containing the murine IFN-gamma cDNA (AdmIFN-gamma), and challenged 24 h later with Af. We observed that i.n. administration of AdmIFN-gamma resulted in about a fourfold increase in levels of IFN-gamma and IL-12 within the lung, about a 75% reduction in lung fungal contents at day 2 and a more than threefold higher survival rate in the AdmIFN-gamma-treated group compared to the controls (P < 0.01). This protection effect was not found when AdmIFN-gamma was i.p. administrated. Alveolar macrophages and lung leucocytes isolated from i.n. AdmIFN-gamma-treated animals displayed enhanced killing of intracellular Aspergillus organisms ex vivo. These results demonstrate that transient overexpression of IFN-gamma could augment host defence against Aspergillus.
authors.affiliation: Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: C
authors.initials: C
authors.lastname: Shao
authors.forename: J
authors.initials: J
authors.lastname: Qu
authors.forename: L
authors.initials: L
authors.lastname: He
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Zhou
authors.forename: X
authors.initials: X
authors.lastname: Liu
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001228:Aspergillosis / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D001232:Aspergillus fumigatus / Q000302:isolation & purification*; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D015316:Genetic Therapy / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology; D008172:Lung Diseases, Fungal / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration; D010587:Phagocytosis / Q000276:immunology
chemical_list: D007371:Interferon-gamma