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.
Shinozawa
Yoko
Y
Matsumoto
Tetsuya
T
Second Department of Internal Medicine, *Department of Microbiology and †Department of Hospital Pathology, Toho University School of Medicine, 5-21-16 Omori-Nishi, Ota-ku, Tokyo, 143-8540 and ‡Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Uchida
Kou
K
Tsujimoto
Shiro
S
Second Department of Internal Medicine, *Department of Microbiology and †Department of Hospital Pathology, Toho University School of Medicine, 5-21-16 Omori-Nishi, Ota-ku, Tokyo, 143-8540 and ‡Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Iwakura
Yoichiro
Y
Second Department of Internal Medicine, *Department of Microbiology and †Department of Hospital Pathology, Toho University School of Medicine, 5-21-16 Omori-Nishi, Ota-ku, Tokyo, 143-8540 and ‡Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Yamaguchi
Keizo
K
Second Department of Internal Medicine, *Department of Microbiology and †Department of Hospital Pathology, Toho University School of Medicine, 5-21-16 Omori-Nishi, Ota-ku, Tokyo, 143-8540 and ‡Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
D000818:Animals; D016207:Cytokines / Q000032:analysis / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D007375:Interleukin-1 / Q000032:analysis / Q000097:blood; D016952:Legionella pneumophila; D007877:Legionnaires' Disease / Q000097:blood / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma