1887

Abstract

can infect dendritic cells (DCs), but the molecular mechanism by which these cells contribute to tuberculosis pathogenesis is largely unclear. Using and the attenuated strain BCG as model strains, we analysed cytokine and chemokine secretion in murine DCs infected with 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 promoted secretion of IL-1β, IL-10 and IL-23. Heat-killed BCG and 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 gave high expression of foxp3 and IL-10, directing differentiation of naïve CD4 T cells into regulatory T cells (CD4CD25Foxp3) more effectively than BCG. Furthermore, -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.

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2013-02-01
2019-12-06
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