Host genetic background determines whether IL-18 deficiency results in increased susceptibility or resistance to murine Leishmania major infection

doi:10.1016/j.imlet.2004.04.001

Immunology Letters

Volume 94, Issues 1–2, 15 June 2004, Pages 35-37

https://doi.org/10.1016/j.imlet.2004.04.001 Get rights and content

Abstract

Interleukin-18 (IL-18) plays an important role in innate and acquired immunity. IL-18 gene deficient (IL-18-/-) mice of the 129×CD1 strain were reported to be more susceptible to Leishmania major infection than the wild-type mice. In contrast IL-18-/- mice of the C57BL/6 background were found to be as resistant as the wild-type (WT) mice. To resolve this discrepancy, IL-18 gene deficiency was introduced by backcrossing on to the highly susceptible BALB/c, or the moderately resistant DBA/1 backgrounds. Here we have demonstrated that BALB/c IL-18-/- mice were more resistant to L. major infection than WT BALB/c mice, whereas DBA/1 IL-18-/- mice were markedly more susceptible than their WT littermates. BALB/c IL-18-/- mice produced less IFNγ and IL-4, whereas DBA/1 IL-18ko mice produced more IFNγ and IL-4 than their respective WT controls. These result clearly demonstrate that the role of IL-18 in resistance or susceptibility to L. major is determined by host genetic background.

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Acknowledgements

This work received financial support from The Arthritis Research Campaign, the Wellcome Trust, the Medical Research Council, and the Chief Scientist’s Office, Scotland. W. Niedbala was also supported by the Committee of Scientific Research and Ministry of Health of Poland (Grant No. 4PO5BO1319).

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Citation Excerpt :
In highly resistant C57BL/6 mice that generate potent Th1 responses during L. major infection, IL-18 apparently plays a minor role in protection against murine leishmaniasis so that IL-18-deficient C56BL/6 mice exhibit larger sores than the mice in early infection, but they eventually recover from the disease. In other mouse strains that have a moderate resistance to L. major infection such as 129xC1 and DBA/1 mice, IL-18 acts as an indispensable mediator to defeat Leishmania infection [73]. Conversely, in susceptible BALB/c mice, a Th2 response is generated during Leishmania infection, which may result from the lack of continuous IL-12 production [73].
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Short communicationHost genetic background determines whether IL-18 deficiency results in increased susceptibility or resistance to murine Leishmania major infection

Abstract

Section snippets

Acknowledgements

Immunity

Immunity

IFNγ-inducing factor (IGIF) is a costimulatory factor on the activation of Th1 but not Th2 cells and exerts its effect independently of IL-12

J. Immunol.

IL-18 is a potent coinducer of IL-13 in NK and T cells: a new potential role for IL-18 in modulating the immune response

J. Immunol.

IL-18 induces the differentiation of Th1 or Th2 cells depending upon cytokine milieu and genetic background

Eur. J. Immunol.

IL-18 induction of IgE: dependence on CD4+ T cells, IL-4 and STAT6

Nat. Immunol.

Interleukin-18 regulates both Th1 and Th2 responses

Annu. Rev. Immunol.

Short communication
Host genetic background determines whether IL-18 deficiency results in increased susceptibility or resistance to murine Leishmania major infection