engleski

The role of IFN-gamma receptor in the control and clearance of Legionella micdadei from its experimental murine host

Legionella micdadei (Pittsburgh pneumonia agent) is commonly identified as a cause of nosocomial infection. Illness due to L. micdadei occurs in heart and kidney transplant patients, HIV-infected patients and other immunocompromised patients. Since the infections by L. micdadei occurs predominantly in immunocompromised hosts, we examined the virulence of L. micdadei in immunodeficient IFN-gamma receptor knockout mice. We explored the kinetics of bacterial clearence and patohistological changes in IFN-gR -/- and control C57Bl/6 mice. Pathogen-free 6- to 10-weeks-old IFN-gR -/- and C57Bl/6 mice were infected by intratracheal inoculation with L. micdadei (clinical isolate) using a dose of 10^7 CFU. We determined the mortality rate and bacterial clearence from the lungs, livers and spleens of infected mice at different time points post infection. We also followed the patohistological changes in these organs during 168 hours of infection. Our results showed a higher mortality rate of IFN-gR -/- mice in comparison to control C57Bl/6 mice. After intratracheal inoculation of 10^7 CFU of L. micdadei all IFN-gR -/- mice died within 12 days, while control mice survived the infection. The numbers of L. micdadei recovered from the lungs of IFN-gR -/- mice were significantly higher compared to the control C57Bl/6 mice. At day 7 post infection L. micdadei was not detected in the spleens and livers of C57Bl/6 mice, whereas, IFN-gR -/- mice showed signs of systemic bacterial infection. In comparison to C57Bl/6 mice, IFN-gR -/- showed significantly higher infiltration of inflammatory cells on the 3rd day of infection with progression of disease on 7th day. IFN-gR -/- mice developed severe bronchopneumonia with infiltration of interstitial tissue, while control mice showed only mild peribronchial inflammatory cell infiltration. Nods of inflammatory cells were present in the liver of IFN-gR -/- mice from day 3 after infection in contrast to control mice which cleared the bacteria. In this study we demonstrate a critical role of IFN-gR in the control and clearance of L. micdadei from mice. IFN-gR-/- mice failed to control L. micdadei and eventually succumbed to an overwhelming bacterial burden.

Legionella micdadei; immunocompromised host; IFN-gamma receptor

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