Host genetic background determines whether IL-18 deficiency results in increased susceptibility or resistance to murine Leishmania major infection.
Interleukin-18 (IL-18) plays an important role in innate and acquired immunity. IL-18 gene deficient (IL-18-/-) mice of the 129 x 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 IFNgamma and IL-4, whereas DBA/1 IL-18ko mice produced more IFNgamma 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.
Wei
Xiao-Qing
XQ
Division of Immunology, Infection and Inflammation, University of Glasgow, Western Infirmary, Glasgow, Scotland G11 6NT, UK. xqw1r@clinmed.gla.ac.uk
Niedbala
Wanda
W
Xu
Damo
D
Luo
Zhao-Xia
ZX
Pollock
Kevin G J
KG
Brewer
James M
JM
D000818:Animals; D004198:Disease Susceptibility / Q000276:immunology; D007371:Interferon-gamma / Q000032:analysis; D020382:Interleukin-18 / Q000235:genetics*; D015847:Interleukin-4 / Q000032:analysis; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000235:genetics* / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology
D020382:Interleukin-18; D015847:Interleukin-4; D007371:Interferon-gamma