The adjuvant activity of CpG DNA requires T-bet expression in dendritic cells
The adjuvant activity of CpG DNA requires T-bet expression in dendritic cells
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DOI：
10.1073/pnas.0506638102
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发表时间：
2005-09-13
影响因子：
11.1
通讯作者：
Glimcher, LH
中科院分区：
文献类型：
--
作者：
Lugo-Villarino, G;Ito, S;Glimcher, LH
用含有CpG基序的合成寡脱氧核苷酸（CpG ODN）进行治疗对原本致命的感染具有显著的保护作用。在此，我们描述了转录因子T - bet在介导CpG ODN保护功能中的关键作用。常规的CD11c（高）树突状细胞（DC）和浆细胞样DC中T - bet的缺失会损害干扰素的产生。令人惊讶的是，与Rag2（-/-）小鼠不同，同时缺乏T - bet的Rag2（-/-）小鼠（双敲除，DKO）不能通过预先用CpG ODN治疗从单核细胞增生李斯特菌的致命感染中获救。通过从野生型（WT）但不是T - bet（-/-）且经CpG ODN治疗的供体小鼠过继转移CD11c（高）DC可实现挽救。我们得出结论，DC中的T - bet是CpG ODN在感染中的佐剂活性所必需的，这揭示了它在先天免疫中的重要作用。
Treatment with synthetic oligodeoxynucleotides containing CpG motifs (CpG ODNs) is remarkably protective against otherwise lethal infection. Here, we describe an essential role for the transcription factor T-bet in mediating the protective function of CpG ODNs. Loss of T-bet in conventional CD11c(hi) dendritic cells (DCs) and in plasmacytoid DCs impaired production of IFNs. Strikingly, in contrast to Rag2(-/-) mice, Rag2(-/-) mice that also lacked T-bet (DKO) could not be rescued from lethal Listeria monocytogenes infection by prior treatment with CpG ODN. Rescue was achieved by adoptive transfer of CD11c(hi) DCs from WT, but not T-bet(-/-), CpG ODN-treated donor mice. We conclude that T-bet in DCs is required for the adjuvant activity of CpG ODN in infection, revealing its vital role in innate immunity.