title: Mycobacterium bovis and BCG induce different patterns of cytokine and chemokine production in dendritic cells and differentiation patterns in CD4+ T cells.
abstract: Mycobacterium tuberculosis can infect dendritic cells (DCs), but the molecular mechanism by which these cells contribute to tuberculosis pathogenesis is largely unclear. Using Mycobacterium bovis and the attenuated strain M. bovis BCG as model strains, we analysed cytokine and chemokine secretion in murine DCs infected with M. bovis and BCG at 6, 12 and 24 h post-infection. BCG enhanced production of MCP-1, RANTES, IL-12, TNF-α and IL-6 in DCs, while M. bovis promoted secretion of IL-1β, IL-10 and IL-23. Heat-killed BCG and M. bovis both stimulated cytokine production, but at significantly lower concentrations than corresponding live bacteria. Quantitative RT-PCR and Western blotting indicated that NF-κB regulates production of most cytokines and chemokines. After DCs were infected for 24 h, the culture was used to activate naïve CD4(+) T cells. A combination of the supernatant and activated DCs infected with M. bovis gave high expression of foxp3 and IL-10, directing differentiation of naïve CD4(+) T cells into regulatory T cells (CD4(+)CD25(+)Foxp3(+)) more effectively than BCG. Furthermore, M. bovis-infected DC cultures induced CD4(+) T cells to express significantly higher levels of IL-17, a Th17-type cytokine, while BCG-infected DC cultures stimulated an apparently higher production of IFN-γ, a Th1-type cytokine. In addition, the mycobacteria did not exert a direct effect on the differentiation of CD4(+) T cells. These differential cytokine profiles in DCs and CD4(+) T cells, and the resultant development of CD4(+) T subsets, may be related to the pathogenesis of tuberculosis.
authors.affiliation: College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.|The National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Xiansong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.|The National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.|The National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Luo
authors.affiliation: College of Animal Science, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Yingyu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.|The National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Shi
authors.initials: S
authors.lastname: Cheng
authors.affiliation: College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.|The National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Changmin
authors.initials: C
authors.lastname: Hu
authors.affiliation: College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.|The National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Huanchun
authors.initials: H
authors.lastname: Chen
authors.affiliation: College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.|The National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Aizhen
authors.initials: A
authors.lastname: Guo
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology*; D018925:Chemokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology*; D020869:Gene Expression Profiling; D051379:Mice; D009163:Mycobacterium bovis / Q000276:immunology* / Q000472:pathogenicity; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D018925:Chemokines