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Decreased Susceptibility of Mice to Infection with Listeria monocytogenes in the Absence of Interleukin-18
- Lochner, Matthias, Kastenmüller, Kathrin, Neuenhahn, Michael, Weighardt, Heike, Busch, Dirk H., Reindl, Wolfgang, Förster, Irmgard
- Infection and immunity 2008 v.76 no.9 pp. 3881-3890
- Listeria monocytogenes, animal models, apoptosis, bacteria, immune response, interferon-gamma, interleukin-18, leukocytes, listeriosis, mice, neutralizing antibodies, spleen, tumor necrosis factor-alpha
- The induction of proinflammatory cytokines such as gamma interferon (IFN-γ) 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-γ, 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.