CpG DNA has immunomodulatory effects, such as the suppression of allergic responses mediated by type II T cell help (TH2). Here we report that CpG, but not lipopolysaccharide (LPS), rapidly induces expression of T-bet mRNA in purified B cells. Up-regulation of T-bet by CpG is abrogated in mice deficient in Toll-like receptor 9 (TLR9) and MyD88, but remains intact in B cells deficient in STAT1 (signal transducer and activator of transcription 1). Interleukin 12 (IL-12) alone does not up-regulate T-bet mRNA, but greatly enhances CpG-induced T-bet expression. Furthermore, CpG inhibits immunoglobulin G1 (IgG1) and IgE switching induced by IL-4 and CD40 signaling in purified B cells, and this effect correlates with up-regulation of T-bet. Thus, CpG triggers anti-allergic immune responses by directly regulating T-bet expression via a signaling pathway in B cells that is dependent upon TLR9, independent of interferon-γ (IFN-γ)-STAT1 and synergistic with IL-12.
*Note: In the version of this article initially published online, some of the nomenclature was incorrect. This has been corrected for the HTML and print versions of the article.
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We thank K. Nakashima and Y. Manabe for experimental assistance and J. Encinas for valuable discussions.
The authors declare no competing financial interests.
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