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Laboratories of
*
Parasitic Diseases and
Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
This study documents a defect in IL-12-dependent IFN-
responses
in a substrain (B10.Q-H2-q/SgJ) of B10.Q mice that
manifests as an acute susceptibility to infection by the intracellular
protozoan pathogen, Toxoplasma gondii. Despite robust
systemic production of IL-12, infected B10.Q/J animals fail to mount an
early IFN- response after parasite inoculation. Genetic experiments
revealed that the host resistance and IFN- production defects are
determined by a single autosomal recessive locus distinct from the
Stat4 gene. Nonetheless, a delayed IL-12-mediated IFN-
response emerges in later stages of acute infection but is unable to
prevent host mortality. IL-18 administration restores, in an
IL-12-dependent manner, the early IFN- response and host resistance
of B10.Q/J animals. These in vivo studies indicate that the partially
impaired IL-12 responsiveness in B10.Q/J mice can result in defective
host resistance and demonstrate a therapeutic function for IL-18 in
reversing a genetically based immunodeficiency in IL-12-dependent
IFN- production.
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