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Eur J Immunol. 2015 Jul;45(7):1972-9. doi: 10.1002/eji.201445045. Epub 2015 May 12.

Adaptive immune-mediated host resistance to Toxoplasma gondii is governed by the NF-κB regulator Bcl-3 in dendritic cells.

Author information

1
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
2
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.

Abstract

The atypical IκB family member Bcl-3 associates with p50/NF-κB1 or p52/NF-κB2 homodimers in nuclei, thereby either positively or negatively modulating transcription in a context-dependent manner. Previously we reported that Bcl-3 was critical for host resistance to Toxoplasma gondii. Bcl-3-deficient mice succumbed within 3-5 weeks after infection, correlating with an apparently impaired Th1-type adaptive immune response. However in which cell type(s) Bcl-3 functioned to assure resistance remained unknown. We now show that Bcl-3 expression in dendritic cells is required to generate a protective Th1-type immune response and confer resistance to T. gondii. Surprisingly, mice lacking Bcl-3 in dendritic cells were as susceptible as mice globally deficient for Bcl-3. Furthermore, early innate defenses were not compromised by the absence of Bcl-3, as initial production of IL-12 by dendritic cells and IFN-γ by NK cells were preserved. However, subsequent production of IFN-γ by CD4(+) and CD8(+) T-cells was compromised when dendritic cells lacked Bcl-3, and these mice succumbed at a time when T-cell-mediated IFN-γ production was essential for host resistance. These findings demonstrate that Bcl-3 is required in dendritic cells to prime protective T-cell-mediated immunity to T. gondii.

KEYWORDS:

Adaptive immunity; Bcl-3; Dendritic cells; IFN-γ; T-cells; T. gondii

PMID:
25884683
DOI:
10.1002/eji.201445045
[Indexed for MEDLINE]
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