Altered immune responses and susceptibility to Leishmania major and Staphylococcus aureus infection in IL-18-deficient mice

Wei, Xiao-Qing ORCID: https://orcid.org/0000-0002-6274-8503, Leung, Bernard P., Niedbala, Wanda, Piedrafita, David, Feng, Gui-jie, Sweet, Matt, Dobbie, Lorraine, Smith, Andrew J. H. and Liew, Roo Y. 1999. Altered immune responses and susceptibility to Leishmania major and Staphylococcus aureus infection in IL-18-deficient mice. The Journal of Immunology 163 (5) , pp. 2821-2828.

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Abstract

IL-18, formerly designated IFN-inducing factor, is a novel cytokine produced by activated macrophages. It synergizes with IL-12 in the induction of the development of Th1 cells and NK cells. To define the biological role of IL-18 in vivo, we have constructed a strain of mice lacking IL-18. Homozygous IL-18 knockout (−/−) mice are viable, fertile, and without evident histopathologic abnormalities. However, in contrast to the heterozygous (+/−) or wild-type (+/+) mice, which are highly resistant to the infection of the protozoan parasite Leishmania major, the IL-18−/− mice are uniformly susceptible. The infected IL-18−/− mice produced significantly lower levels of IFN-γ and larger amounts of IL-4 compared with similarly infected +/− and +/+ mice. In contrast, when infected with the extracellular Gram-positive bacteria Staphylococcus aureus, the IL-18−/− mice developed markedly less septicemia than similarly infected wild-type (+/+) mice. However, the mutant mice developed significantly more severe septic arthritis than the control wild-type mice. This was accompanied by a reduction in the levels of Ag-induced splenic T cell proliferation, decreased IFN-γ and TNF-α synthesis, but increased IL-4 production by the mutant mice compared with the wild-type mice. These results therefore provide direct evidence that IL-18 is not only essential for the host defense against intracellular infection, but it also plays a critical role in regulating the synthesis of inflammatory cytokines, and therefore could be an important target for therapeutic intervention.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Dentistry
Subjects:	Q Science > QR Microbiology > QR180 Immunology
Publisher:	American Association of Immunologists
ISSN:	0022-1767
Last Modified:	21 Oct 2022 09:13
URI:	https://orca.cardiff.ac.uk/id/eprint/35662

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