engleski

The role of innate immune response in murine Legionella micdadei infection

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 KO mice and beta-2 microglobuline KO mice. We explored the kinetics of bacterial clearence and patohistological changes in all mice strains mice. Pathogen-free 6- to 10-weeks-old IFN-gR KO, beta-2 microglobuline KO 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. Our results showed a higher mortality rate of IFN-gR KO mice in comparison to control C57Bl/6 and beta-2 microglobuline KO mice. After intratracheal inoculation of 10^7 CFU of L. micdadei all IFN-gR KO mice died within 12 days, while control and beta-2 microglobuline KO mice survived the infection. In contrast to C57Bl/6 and beta-2 microglobuline KO mice, where the inflammatory cell response is present from day 1 post infection, IFN-gR KO mice show signs of systemic bacterial infection from day 3 post infection. C57Bl/6 and beta-2 microglobuline KO mice resolved the infection, C57Bl/6 mice by 7th and beta-2 microglobuline KO mice by 14th day post infection while IFN-gR KO mice developed severe pneumonia with infiltration of interstitial tissue with no signs of resolving. In this study we demonstrate a critical role of early immune response in the control and clearance of L. micdadei infection in mice, while late immune response

Legionella micdadei; immunocompromised host; IFN-gamma receptor

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