The immune response modifier and agonist S-27609 selectively induces toll-like receptor 7 IL-12 and TNF-α production in CD11c+CD11b+CD8- dendric cells

被引:82
作者
Doxsee, CL [1 ]
Riter, TR [1 ]
Reiter, MJ [1 ]
Gibson, SJ [1 ]
Vasilakos, JP [1 ]
Kedl, RM [1 ]
机构
[1] 3M Pharmaceut, Dept Pharmaceut, St Paul, MN 55144 USA
关键词
D O I
10.4049/jimmunol.171.3.1156
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
IL-12 and TNF-alpha production by dendritic cells (DCs) is a critical step in the initiation of local inflammation and adaptive immune responses. We show in this study that a small molecule immune response modifier that is a Toll-like receptor 7 (TLR7) agonist induces IL-12 and TNF-alpha production from murine CD11c(+)CD11b(+)CD8(-) DCs, a subset not previously known for this activity. Stimulation of these DCs through TLR7 in vivo induces significant cytokine production even 12 h after initial stimulation, as wen as migration of the DC into T cell zones of the lymphoid tissue. In contrast, stimulation through TLR4 and TLR9 induced IL-12 production predominantly from CD8(+) DCs, consistent with previously published data. All TLR stimuli induced the increase in surface expression of the activation markers B7-1, B7-2, and class II in both CD8(+) and CD8(-) DCs, demonstrating that CD8(+) DCs do respond to TLR7-mediated stimuli. To date this is the only known stimuli to induce preferential cytokine production from CD8(-) DCs. Given the efficacy of TLR7 agonists as antiviral agents, the data collectively indicate that stimulation of CD8(-) DCs through TLR7 most likely plays a role in the generation of antiviral immune responses.
引用
收藏
页码:1156 / 1163
页数:8
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