Decreased susceptibility of mice to infection with Listeria monocytogenes in the absence of interleukin-18.
The induction of proinflammatory cytokines such as gamma interferon (IFN-gamma) and tumor necrosis factor alpha is crucial for the early control of bacterial infections. Since interleukin-18 (IL-18) acts as a potent inducer of IFN-gamma, it might play an important role in the induction of a protective immune response in listeriosis. We used a murine model of systemic Listeria monocytogenes infection to study the immune response to these intracellular bacteria in the absence of IL-18. For this purpose, IL-18-deficient mice and mice treated with anti-IL-18 neutralizing antibody were infected with L. monocytogenes, and their innate and adaptive immune responses were compared to those of control mice. Unexpectedly, we found that mice deficient in IL-18 were partially resistant to primary infection with L. monocytogenes. At day 3 after infection, the numbers of listeriae in the livers and spleens of control mice were up to 500 times higher than those in IL-18-deficient or anti-IL-18 antibody-treated mice. In addition, the level of proinflammatory cytokines was markedly reduced in IL-18-deficient mice. Enhanced resistance to L. monocytogenes infection in IL-18-deficient mice was accompanied by increased numbers of leukocytes and reduced apoptosis in the spleen 48 to 72 h after infection. In contrast, control and IL-18-deficient mice showed no significant differences in their abilities to mount a protective L. monocytogenes-specific T-cell response.
Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany.
Matthias
M
Lochner
Kathrin
K
Kastenmüller
Michael
M
Neuenhahn
Heike
H
Weighardt
Dirk H
DH
Busch
Wolfgang
W
Reindl
Irmgard
I
Förster
D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D004198:Disease Susceptibility; D020382:Interleukin-18 / Q000172:deficiency / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D008099:Liver / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D020382:Interleukin-18