Infection Immunology Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.
EMBO Mol Med. 2011 Nov;3(11):652-66. doi: 10.1002/emmm.201100173. Epub 2011 Sep 2.
Staphylococcus aureus is an important human pathogen that can cause long-lasting persistent infections. The mechanisms by which persistent infections are maintained involve both bacterial escape strategies and modulation of the host immune response. So far, the investigations in this area have focused on strategies used by S. aureus to persist within the host. Here, we used an experimental mouse model to investigate the host response to persistent S. aureus infection. Our results demonstrated that T cells, which are critical for controlling S. aureus infection, gradually lost their ability to respond to antigenic stimulation and entered a state of anergy with the progression of infection towards persistence. The T cell hyporesponsiveness was reverted by co-stimulation with the phorbol ester PMA, an activator of protein kinase C, suggesting that a failure in the T cell receptor (TCR)-proximal signalling events underlie the hyporesponsive phenotype. The presence of these anergic antigen-specific T cells may contribute to the failure of the host immune response to promote sterilizing immunity during persistent S. aureus infection and also offers new possibilities for novel immunotherapeutic approaches.
金黄色葡萄球菌是一种重要的人类病原体，可以引起持久的持续性感染。维持持续性感染的机制涉及细菌逃避策略和宿主免疫反应的调节。到目前为止，该领域的研究主要集中在金黄色葡萄球菌在宿主内持续存在所使用的策略上。在这里，我们使用实验小鼠模型研究了宿主对持续性金黄色葡萄球菌感染的反应。我们的结果表明，对于控制金黄色葡萄球菌感染至关重要的 T 细胞随着感染向持续性发展逐渐丧失了对抗原刺激的反应能力，并进入无能状态。用佛波醇酯 PMA 共刺激恢复了 T 细胞的低反应性，PMA 是蛋白激酶 C 的激活剂，这表明 T 细胞受体 (TCR) 近端信号事件的失败是低反应表型的基础。这些无能的抗原特异性 T 细胞的存在可能导致宿主免疫反应在持续性金黄色葡萄球菌感染期间无法促进杀菌免疫，并为新型免疫治疗方法提供了新的可能性。
