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

• Published in: Immunology letters 2004-06, Vol.94 (1), p.35-37
• Main Authors: Wei, Xiao-Qing, Niedbala, Wanda, Xu, Damo, Luo, Zhao-Xia, Pollock, Kevin G.J, Brewer, James M
• Format: Article
• Language: English
• Subjects: Animals; Cytokines; Disease Susceptibility - immunology; Infectious immunity-parasite; Interferon-gamma - analysis; Interleukin-18 - genetics; Interleukin-4 - analysis; Knockout; Leishmania major; Leishmaniasis, Cutaneous - genetics; Leishmaniasis, Cutaneous - immunology; Lymphocyte Activation; Mice; Mice, Knockout; T-Lymphocytes - immunology; Th1/Th2
• ISSN: 0165-2478; 1879-0542
• DOI: 10.1016/j.imlet.2004.04.001

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.