title: Adaptive immune-mediated host resistance to Toxoplasma gondii is governed by the NF-κB regulator Bcl-3 in dendritic cells.
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.
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Tassi
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Estefania
authors.initials: E
authors.lastname: Claudio
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Hongshan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Wanhu
authors.initials: W
authors.lastname: Tang
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Hye-Lin
authors.initials: HL
authors.lastname: Ha
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Sun
authors.initials: S
authors.lastname: Saret
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Sher
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Dragana
authors.initials: D
authors.lastname: Jankovic
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Siebenlist
mesh_terms: D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D007111:Immunity, Cellular / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000276:immunology*; D014122:Toxoplasma; D014124:Toxoplasmosis, Animal / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology*
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631345:Bcl3 protein, mouse; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors
keywords: Adaptive immunity; Bcl-3; Dendritic cells; IFN-γ; T-cells; T. gondii