IL-27 signaling compromises control of bacterial growth in mycobacteria-infected mice

被引:110
作者
Pearl, JE
Khader, SA
Solache, A
Gilmartin, L
Ghilardi, N
deSauvage, F
Cooper, AM
机构
[1] Trudeau Inst Inc, Saranac Lake, NY 12983 USA
[2] Genentech Inc, San Francisco, CA 94080 USA
关键词
D O I
10.4049/jimmunol.173.12.7490
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Resistance to tuberculosis (TB) is dependent on the induction of Ag-specific CD4 Th1 T cells capable of expressing IFN-gamma. Generation of these T cells is dependent upon IL-12p70, yet other cytokines have also been implicated in this process. One such cytokine, IL-27, augments differentiation of naive T cells toward an IFN-gamma-producing phenotype by up-regulating the transcription factor T-bet and promoting expression of the IL-12Rbeta2 chain allowing T cells to respond to IL-12p70. We show that the components of IL-27 are induced during TB and that the absence of IL-27 signaling results in an altered disease profile. In the absence of the IL-27R, there is reduced bacterial burden and an increased lymphocytic character to the TB granuloma. Although the number of Ag-specific CD4 IFN-gamma-producing cells is unaffected by the absence of the IL-27R, there is a significant decrease in the level of mRNA for IFN-gamma and T-bet within the lungs of infected IL-27R(-/-) mice. Ag-specific CD4 T cells in the lungs of IL-27R(-/-) also produce less IFN-gamma protein per cell. The data show that expression of IL-27 during TB is detrimental to the control of bacteria and that although it does not affect the number of cells capable of producing IFN-gamma it does reduce the ability of CD4 T cells to produce large amounts of IFN-gamma. Because IFN-gamma is detrimental to the survival of effector T cells, we hypothesize that the reduced IFN-gamma within the IL-27R(-/-) lung is responsible for the increased accumulation of lymphocytes within the mycobacterial granuloma.
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收藏
页码:7490 / 7496
页数:7
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