The NF-kappa B family member RelB is required for innate and adaptive immunity to Toxoplasma gondii.
The NF-kappa 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-kappa B activity that included the NF-kappa 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-gamma plus LPS or TNF-alpha 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-gamma 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-gamma. 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-gamma and resistance to T. gondii.
Caamaño
J
J
Department of Pathobiology, University of Pennsylvania, Philadelphia 19104, USA.
Alexander
J
J
Craig
L
L
Bravo
R
R
Hunter
C A
CA
D000818:Animals; D002469:Cell Separation; D004198:Disease Susceptibility; D005260:Female; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis / Q000172:deficiency; D007376:Interleukin-2 / Q000096:biosynthesis / Q000172:deficiency; D015847:Interleukin-4 / Q000096:biosynthesis / Q000172:deficiency; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D016328:NF-kappa B / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology* / Q000378:metabolism; D014123:Toxoplasmosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D007376:Interleukin-2; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; C497594:Relb protein, mouse; D014157:Transcription Factors; D051841:Transcription Factor RelB; D015847:Interleukin-4; D007371:Interferon-gamma