Protection against pulmonary infection with Klebsiella pneumoniae in mice by interferon-gamma through activation of phagocytic cells and stimulation of production of other cytokines.
The study was designed to determine the role of interferon (IFN)-gamma in inflammatory responses against experimentally induced pneumonia caused by Klebsiella pneumoniae. The host immunological responses in IFN-gamma gene knockout (IFN-gamma(-/-)) mice and immunocompetent control mice were compared. K. pneumoniae strain T-113 was inoculated intranasally into anaesthetised mice to induce pneumonia. Infected control mice survived significantly longer than infected IFN-gamma(-/-) mice. Viable bacterial counts in lungs and blood abruptly increased in IFN-gamma(-/-) mice; in contrast, a gradual decrease in the number of bacteria was noted in control mice. During the early stages of infection, the concentrations of interleukin (IL)-1beta and IL-6 in broncho-alveolar lavage fluid and IL-1beta in serum of IFN-gamma(-/-) mice were significantly lower than in control mice. During the late stage of infection, serum IL-6 level in IFN-gamma(-/-) mice was significantly higher than in control mice. These results suggest that the defective immunological host response, including inflammatory cytokine production caused by deficiency of IFN-gamma, is one of the mechanisms that allow the progression of pulmonary infection to systemic septicaemia.
Yoshida
Kanako
K
Matsumoto
Tetsuya
T
Departments of Internal Medicine II, *Microbiology and †Hospital Pathology, Toho University School of Medicine, Omori-Hishi, Ota-ku, Tokyo and ‡Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Tateda
Kazuhiro
K
Departments of Internal Medicine II, *Microbiology and †Hospital Pathology, Toho University School of Medicine, Omori-Hishi, Ota-ku, Tokyo and ‡Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Uchida
Kou
K
Tsujimoto
Shiro
S
Departments of Internal Medicine II, *Microbiology and †Hospital Pathology, Toho University School of Medicine, Omori-Hishi, Ota-ku, Tokyo and ‡Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Iwakura
Yoichiro
Y
Departments of Internal Medicine II, *Microbiology and †Hospital Pathology, Toho University School of Medicine, Omori-Hishi, Ota-ku, Tokyo and ‡Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Yamaguchi
Keizo
K
Departments of Internal Medicine II, *Microbiology and †Hospital Pathology, Toho University School of Medicine, Omori-Hishi, Ota-ku, Tokyo and ‡Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015169:Colony Count, Microbial; D016207:Cytokines / Q000032:analysis / Q000097:blood; D004195:Disease Models, Animal; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D007700:Kinetics; D007710:Klebsiella Infections / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D007711:Klebsiella pneumoniae / Q000276:immunology* / Q000302:isolation & purification; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010586:Phagocytes / Q000276:immunology*; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology / Q000401:mortality
D016207:Cytokines; D007371:Interferon-gamma