Reduced host resistance and Th1 response to Cryptococcus neoformans in interleukin-18 deficient mice.
Using interleukin (IL)-18 deficient (IL-18(-/-)) mice, we examined the role of IL-18 in the host resistance and Th1 response against infection with Cryptococcus neoformans. Fungal clearance in the lung was reduced in IL-18(-/-) mice, although there was no significant change in the level of dissemination to the brain. The DTH response, as determined by footpad swelling, was also diminished in IL-18(-/-) mice compared to control wild-type (WT) mice. The levels of IL-12 and interferon (IFN)-gamma in the sera were significantly lower in IL-18(-/-) mice than in WT mice. Spleen cells from infected WT mice produced a high level of IFN-gamma upon stimulation with the microbe, while only a low level of IFN-gamma production was detected in spleen cells from infected IL-18(-/-) mice. Administration of IL-18 almost completely restored the reduced response in IL-18(-/-) mice, while IL-12 showed a marginal effect. These results demonstrated the important role of IL-18 in the resistance and Th1 response of mice to C. neoformans by potentiating the production of IFN-gamma.
Kawakami
K
K
First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, Japan. kawakami@med.u-ryukyu.ac.jp
Koguchi
Y
Y
Qureshi
M H
MH
Kinjo
Y
Y
Yara
S
S
Miyazato
A
A
Kurimoto
M
M
Takeda
K
K
Akira
S
S
Saito
A
A
D000818:Animals; D001921:Brain / Q000276:immunology / Q000382:microbiology; D015169:Colony Count, Microbial; D003433:Crosses, Genetic; D003453:Cryptococcosis / Q000276:immunology* / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000276:immunology* / Q000302:isolation & purification; D016207:Cytokines / Q000097:blood; D006968:Hypersensitivity, Delayed / Q000503:physiopathology; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D020382:Interleukin-18 / Q000097:blood / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D016207:Cytokines; D020382:Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma