Adaptive immune-mediated host resistance to Toxoplasma gondii is governed by the NF-[kappa]B regulator Bcl-3 in dendritic cells

• Published in: European journal of immunology Vol. 45; no. 7; pp. 1972 - 1979
• Main Authors: Tassi, Ilaria, Claudio, Estefania, Wang, Hongshan, Tang, Wanhu, Ha, Hye-lin, Saret, Sun, Sher, Alan, Jankovic, Dragana, Siebenlist, Ulrich
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 01-07-2015
• Subjects: Antigens; Dendritic cells; Rodents; T cell receptors; Toxoplasma gondii
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201445045

The atypical I[kappa]B family member Bcl-3 associates with p50/NF-[kappa]B1 or p52/NF-[kappa]B2 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-[gamma] by NK cells were preserved. However, subsequent production of IFN-[gamma] 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-[gamma] 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.