| First Author | Tassi I | Year | 2015 |
| Journal | Eur J Immunol | Volume | 45 |
| Issue | 7 | Pages | 1972-9 |
| PubMed ID | 25884683 | Mgi Jnum | J:229781 |
| Mgi Id | MGI:5754455 | Doi | 10.1002/eji.201445045 |
| Citation | Tassi I, et al. (2015) Adaptive immune-mediated host resistance to Toxoplasma gondii is governed by the NF-kappaB regulator Bcl-3 in dendritic cells. Eur J Immunol 45(7):1972-9 |
| abstractText | The atypical IkappaB family member Bcl-3 associates with p50/NF-kappaB1 or p52/NF-kappaB2 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. |
