Transient overexpression of γ interferon promotes Aspergillus clearance in invasive pulmonary aspergillosis

Cytokines are critical molecules necessary for normal lung pathogen host defences. Gamma interferon (IFN-γ) and T1-phenotype immune responses are important components of host defence against Aspergillus. Therefore, we hypothesized that transient overexpression of IFN-γ within the lung could augment host immunity against Aspergillus. Here it was showed that intranasal administration of 5 × 10⁷ colony-forming units (CFU) of Aspergillus fumigatus (Af) induced the expression of IFN-γ. Mice were intranasally (i.n) administrated with 5 × 10⁸ PFU of a recombinant adenovirus vector containing the murine IFN-γ cDNA (AdmIFN-γ), and challenged 24 h later with Af. We observed that i.n. administration of AdmIFN-γ resulted in about a fourfold increase in levels of IFN-γ 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-γ-treated group compared to the controls (P < 001). This protection effect was not found when AdmIFN-γ was i.p. administrated. Alveolar macrophages and lung leucocytes isolated from i.n. AdmIFN-γ- treated animals displayed enhanced killing of intracellular Aspergillus organisms ex vivo. These results demonstrate that transient overexpression of IFN-γ could augment host defence against Aspergillus.