Antibody-Opsonized Bacteria Evoke an Inflammatory Dendritic Cell Phenotype and Polyfunctional Th Cells by Cross-Talk between TLRs and FcRs
Antibody-Opsonized Bacteria Evoke an Inflammatory Dendritic Cell Phenotype and Polyfunctional Th Cells by Cross-Talk between TLRs and FcRs
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DOI：
10.4049/jimmunol.1303126
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发表时间：
2015-02-15
影响因子：
4.4
通讯作者：
van Egmond, Marjolein
中科院分区：
文献类型：
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作者：
Bakema, Jantine E.;Tuk, Cornelis W.;van Egmond, Marjolein
在二次免疫反应期间，Ab 调理细菌通过 FcR 被树突状细胞有效吸收。我们现在证明，这一过程会诱导 FcR 和 TLR 之间的串扰，从而导致几种炎症细胞因子的协同释放，以及脂质代谢谱的改变。这种改变的炎症特征将 Th1 极化转向 Th17 细胞反应。有趣的是，产生 GM-CSF 的 Th 细胞也被协同诱发，这表明多功能 Th17 细胞的出现。细胞因子的协同释放取决于分别通过 TLR 和 FcR 的 MyD88 和 ITAM 信号通路的激活。细胞因子调节通过 TNF-α 和 IL-23 的转录依赖性机制以及 IL-1 β 的 caspase-1 依赖性释放的转录后机制发生。此外，TLR 和 FcR 之间的串扰并不限于树突状细胞。总之，我们的结果支持，与 Ab 调理细菌相比，单独的细菌通过两类受体的联合作用启动了根本不同的免疫反应，并最终可能改进炎症性疾病的新疗法。
During secondary immune responses, Ab-opsonized bacteria are efficiently taken up via FcRs by dendritic cells. We now demonstrate that this process induces cross-talk between FcRs and TLRs, which results in synergistic release of several inflammatory cytokines, as well as altered lipid metabolite profiles. This altered inflammatory profile redirects Th1 polarization toward Th17 cell responses. Interestingly, GM-CSF-producing Th cells were synergistically evoked as well, which suggests the onset of polyfunctional Th17 cells. Synergistic cytokine release was dependent on activation via MyD88 and ITAM signaling pathways through TLRs and FcRs, respectively. Cytokine regulation occurred via transcription-dependent mechanisms for TNF-alpha and IL-23 and posttranscriptional mechanisms for caspase-1-dependent release of IL-1 beta. Furthermore, cross-talk between TLRs and FcRs was not restricted to dendritic cells. In conclusion, our results support that bacteria alone initiate fundamentally different immune responses compared with Ab-opsonized bacteria through the combined action of two classes of receptors and, ultimately, may refine new therapies for inflammatory diseases.