Role of interferon-gamma in inflammatory responses in murine respiratory infection with Legionella pneumophila

The role of interferon (IFN)-gamma in host inflammatory responses, including inflammatory cytokine production, in experimental pneumonia with Legionella pneumophila was examined in IFN-gamma knockout (IFN-gamma(-/-)) mice. IFN-gamma(-/-) mice and wild-type BALB/cA mice were inoculated intranasally with L. pneumophila strain KC. The survival rate of IFN-gamma(-/-) mice was significantly lower than that of control mice. Viable bacterial counts in lungs and blood showed a rapid and continuous increase in IFN-gamma(-/-) mice, in contrast to a gradual decrease in the lungs and an intermittent bacteraemia in control mice. Histopathological analysis of L. pneumophila-infected lung tissues demonstrated mild pneumonia in control mice, whereas severe pneumonia was shown in IFN-gamma(-/-) mice. During the late stages of infection, the number of total bronchoalveolar lavage (BAL) cells was significantly higher in IFN-gamma(-/-) than in control mice. The concentrations of tumour necrosis factor-alpha and interleukin-1beta in sera of IFN-gamma(-/-) mice were significantly lower in control mice during the early stages of infection, suggesting suppressed production of inflammatory cytokines in IFN-gamma(-/-) mice. In contrast, during the late stages of infection, the levels of these cytokines were significantly higher in sera of IFN-gamma(-/-) mice than in control mice, suggesting severe and systemic infection in IFN-gamma(-/-) mice. The findings suggest that retardation of host immune responses, including inflammatory cytokine production caused by deficiency of IFN-gamma, might allow the bacteria to grow and cause fulminant pneumonia.