Mandron Marie, Ariès Marie-Françoise, Brehm Rossalyn D, Tranter Howard S, Acharya K Ravi, Charveron Marie, Davrinche Christian
Institut National de la Santé et de la Recherche Médicale, INSERM, U563, Toulouse, France.
J Allergy Clin Immunol. 2006 May;117(5):1141-7. doi: 10.1016/j.jaci.2005.12.1360. Epub 2006 Apr 4.
Immune surveillance against microbes at sites of interface with environment involves immediate recognition of pathogen-associated molecular patterns by dendritic cells (DCs). According to their first-line position, DCs are key parameters for the establishment of an appropriate innate and adaptive response against pathogens to avoid disease development. Even though their role in pathogenesis is well known, bacterial toxins have been less examined for their ability to drive DC activation and T-cell polarization.
We made the assumption that early conditioning of DCs with Staphylococcus aureus enterotoxins could take part in T-cell polarization.
Human monocyte-derived DCs were stimulated with S aureus enterotoxin B (SEB) and characterized with respect to secretion of inflammatory cytokines and their ability to drive polarization of naive allogenic T cells.
We demonstrated that SEB induced maturation of DCs and that SEB-activated DCs secreted high levels of IL-2 but no IL-12p70, contrary to LPS-activated ones. Accordingly, we further showed that SEB-activated DCs were able to drive polarization of naive T cells into the T(H)2 subset. By using highly purified SEB and Toll-like receptor (TLR)-2 stably transfected Human Embryonic Kidney (HEK) 293 cells, we demonstrated for the first time the ability of SEB to induce TLR2 signaling. Furthermore, the involvement of SEB-TLR2 interaction in activation of dendritic cells was supported by neutralizing activity of anti-TLR2 antibodies.
Altogether, our findings reinforce the notion that bacterial toxins may appear as new pathogen-associated molecular patterns, which could play a major role in inflammation and bacterial pathologies.
在与环境的界面处对微生物进行免疫监视涉及树突状细胞（DCs）对病原体相关分子模式的即时识别。鉴于其一线位置，DCs是建立针对病原体的适当先天性和适应性反应以避免疾病发展的关键参数。尽管它们在发病机制中的作用已广为人知，但细菌毒素驱动DC激活和T细胞极化的能力却较少受到研究。
我们假设用金黄色葡萄球菌肠毒素对DCs进行早期预处理可能参与T细胞极化。
用人单核细胞衍生的DCs用金黄色葡萄球菌肠毒素B（SEB）刺激，并就炎性细胞因子的分泌及其驱动幼稚同种异体T细胞极化的能力进行表征。
我们证明SEB诱导DCs成熟，并且与LPS激活的DCs相反，SEB激活的DCs分泌高水平的IL-2但不分泌IL-12p70。因此，我们进一步表明SEB激活的DCs能够将幼稚T细胞极化为T(H)2亚群。通过使用高度纯化的SEB和稳定转染Toll样受体（TLR）-2的人胚肾（HEK）293细胞，我们首次证明了SEB诱导TLR2信号传导的能力。此外，抗TLR2抗体的中和活性支持了SEB-TLR2相互作用在树突状细胞激活中的作用。
总之，我们的研究结果强化了这样一种观念，即细菌毒素可能作为新的病原体相关分子模式出现，这可能在炎症和细菌病理学中起主要作用。
