Direct stimulation of tlr5+/+ CD11c+ cells is necessary for the adjuvant activity of flagellin.
Direct stimulation of tlr5+/+ CD11c+ cells is necessary for the adjuvant activity of flagellin.
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DOI：
10.4049/jimmunol.0804225
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发表时间：
2009-06-15
期刊：
影响因子：
--
通讯作者：
Mizel SB
中科院分区：
文献类型：
--
作者：
Bates JT;Uematsu S;Akira S;Mizel SB
鞭毛蛋白是一种非常有效的佐剂，但这种活性的细胞机制仍然不确定。更具体地说，对于鞭毛蛋白是否直接或间接激活树突状细胞（DC），还没有达成共识。用鞭毛蛋白-OVA融合蛋白肌肉内免疫导致体内引流淋巴结中T细胞聚集和OVA特异性CD 4 + T细胞产生IL-2的增强。用鞭毛蛋白-OVA免疫也比用鞭毛蛋白和OVA作为单独的蛋白质免疫触发更高水平的Ag特异性CD 4 + T细胞增殖。为了确定鞭毛蛋白与OVA的融合蛋白是否直接作用于DC，我们使用了CD 4 + T细胞过继转移和骨髓嵌合体小鼠的组合，其中通过注射白喉毒素来控制潜在tlr 5 +/+ CD 11 c+细胞的存在或不存在。与具有来自tlr 5 −/−和野生型背景的DC的小鼠相比，具有来自tlr 5 −/−背景的CD 11 c+细胞和所有其他造血细胞的混合群体的小鼠中的Ag特异性CD 4 + T细胞应答显著降低。MyD 88 −/− tlr 5 +/+小鼠的免疫显示，用鞭毛蛋白-OVA免疫后增强的应答依赖于通过TLR 5-MyD 88途径的信号传导以及通过TLR 5靶向Ag导致的增强的Ag摄取和加工。总之，我们的数据与以下结论一致：直接刺激tlr 5 +/+ CD 11 c+细胞对于鞭毛蛋白融合蛋白的佐剂活性是必需的，并且这种佐剂作用需要通过TLR 5进行信号传导。
Flagellin is a highly effective adjuvant, but the cellular mechanism underlying this activity remains uncertain. More specifically, no consensus exists as to whether flagellin activates dendritic cells (DC) directly or indirectly. Intramuscular immunization with flagellin-OVA fusion protein resulted in enhanced in vivo T cell clustering in draining lymph nodes and IL-2 production by OVA-specific CD4+ T cells. Immunization with flagellin-OVA also triggered greater levels of Ag-specific CD4+ T cell proliferation than immunization with flagellin and OVA as separate proteins. To determine whether flagellin, in the context of a fusion protein with OVA, was acting directly on DC, we used a combination of CD4+ T cell adoptive transfers and bone marrow chimera mice in which the presence or absence of potential tlr5+/+ CD11c+ cells was controlled by injection of diphtheria toxin. The Ag-specific CD4+ T cell response in mice with CD11c+ cells from a tlr5−/− background and mixed populations of all other hematopoietic cells was dramatically reduced in comparison to mice that had DC from tlr5−/− and wild-type backgrounds. Immunization of MyD88−/−tlr5+/+ mice revealed that the enhanced response following immunization with flagellin-OVA is dependent on signaling via the TLR5-MyD88 pathway as well as enhanced Ag uptake and processing resulting from Ag targeting via TLR5. In summary, our data are consistent with the conclusion that direct stimulation of tlr5+/+ CD11c+ cells is necessary for the adjuvant activity of a flagellin fusion protein and that this adjuvant effect requires signaling through TLR5.
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影响因子：
32.4
作者：
Jung, S;Unutmaz, D;Lang, RA
通讯作者：
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64.8
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3.1
作者：
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通讯作者：
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