Transient overexpression of gamma interferon promotes Aspergillus clearance in invasive pulmonary aspergillosis.

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.