The NF-κB Family Member RelB Is Required for Innate and Adaptive Immunity to Toxoplasma gondii

Abstract

The NF-κB 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-κB activity that included the NF-κB 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-γ plus LPS or TNF-α 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-γ 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-γ. 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-γ and resistance to T. gondii.