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B Family Member RelB Is Required for Innate and Adaptive Immunity to Toxoplasma gondii1
*
Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104;
Department of Immunology, The Strathclyde Institute of Biomedical Sciences, University of Strathclyde, Glasgow, Scotland; and
Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543
The NF-
B family of transcription factors are associated with the
regulation of innate and adaptive immunity to infection. Infection of
C57BL/6 mice with Toxoplasma gondii resulted in
up-regulation of NF-B activity that included the NF-B family
member RelB. To assess the role of RelB in the regulation of the immune
response to this infection, we challenged RelB-deficient mice
(RelB-/-) and wild-type (WT) littermate controls with
T. gondii. Although WT controls were resistant to
T. gondii, RelB-/- mice succumbed 10–15
days after infection. Examination of accessory cell functions
associated with resistance to T. gondii revealed that
RelB-/- macrophages stimulated with IFN-
plus LPS or
TNF-
produced IL-12 as well as reactive nitrogen intermediates and
inhibited parasite replication similar to WT macrophages. Analysis of
the systemic responses of RelB-/- and WT mice revealed
that infected mice had similar serum levels of IL-12. However,
RelB-/- mice challenged with T. gondii
produced negligible levels of IFN- and had reduced NK cell activity
compared with WT mice. Similarly, splenocytes from uninfected
RelB-/- mice stimulated with polyclonal stimuli were
deficient in their ability to produce IFN-. Together, our results
demonstrate that RelB is essential for the development of innate NK and
adaptive T cell responses that lead to the production of IFN- and
resistance to T. gondii.
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