Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
Cell Immunol. 2012 Nov;280(1):101-7. doi: 10.1016/j.cellimm.2012.12.001. Epub 2012 Dec 19.
The innate immune system can recognize pathogen-associated molecular patterns (PAMP) through toll-like receptors (TLRs). TLR stimulation by TLR-ligands (TLR-L) induces several genes that can regulate the immune response. In this study, we compared the ability of diverse TLR2-L to activate professional antigen presenting cells (pAPCs). We found that in comparison to whole non-replicating microorganism Mycobacterium butyricum, the smaller components; lipoteichoic acid and Pam3CSK4 significantly enhanced the expression of several pro-inflammatory mediators. These included IL-6, TNF-α and nitric oxide both at the mRNA and the protein levels. Moreover, the higher response was associated with a differential activation of nuclear transcription factor kappa-B (NF-κB) by the diverse TLR2-L. However, all three ligands enhanced antigen cross-presentation and T cell induction after virus infection to the same extent. In conclusion, the data highlight the potential for small components of TLR agonists to induce superior inflammatory immune responses than whole microbial preparation in the field of vaccine studies.
先天免疫系统可以通过 toll 样受体 (TLR) 识别病原体相关分子模式 (PAMP)。TLR 配体 (TLR-L) 刺激 TLR 会诱导几种能够调节免疫反应的基因。在这项研究中,我们比较了不同 TLR2-L 激活专业抗原提呈细胞 (pAPC) 的能力。我们发现,与完整的非复制微生物丁酸分枝杆菌相比,较小的成分脂磷壁酸和 Pam3CSK4 显著增强了几种促炎介质的表达。这些介质包括在 mRNA 和蛋白质水平上的 IL-6、TNF-α 和一氧化氮。此外,更高的反应与不同的 TLR2-L 对核转录因子 kappa-B (NF-κB) 的差异激活有关。然而,所有三种配体在病毒感染后增强了抗原交叉呈递和 T 细胞诱导,程度相同。总之,这些数据强调了 TLR 激动剂的小成分在疫苗研究领域可能比整个微生物制剂诱导更强的炎症免疫反应的潜力。