期刊
JOURNAL OF IMMUNOLOGY
卷 172, 期 8, 页码 4733-4743出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.172.8.4733
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资金
- NIAID NIH HHS [R01 AI48638-01, U19AI057266, R01 AI056499-01] Funding Source: Medline
- NIDCR NIH HHS [DE1391] Funding Source: Medline
- NIDDK NIH HHS [R01 DK 57665-01] Funding Source: Medline
The adaptive immune system can generate distinct classes of responses, but the mechanisms that determine this are poorly understood. In this study, we demonstrate that different Toll-like receptor (TLR) ligands induce distinct dendritic cell (DC) activation and immune responses in vivo. Thus, Escherichia coli LPS (TLR-4 stimulus), activates DCs to produce abundant IL-12(p70), but little IL-10, and stimulates Th1 and Tc1 responses. In contrast, Pam-3-cys (TLR-2 stimulus) elicits less IL-12(p70), but abundant IL-10, and favors Th2 and T cytotoxic 2 (Tc2) responses. These distinct responses likely occur via differences in extracellular signal-regulated kinase signaling in DCs. Thus, Pam-3-cys induces enhanced extracellular signal-regulated kinase signaling, compared with LPS, resulting in suppressed IL-12(p70) and enhanced IL-10 production, as well as enhanced induction of the transcription factor, c-Fos. Interestingly, DCs from c-fos(-/-) mice produce more IL-12(p70), but less IL-10, compared with control DCs. Therefore, different TLR ligands induce distinct cytokines and signaling in DCs, and differentially bias Th responses in vivo.
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