The Staphylococcus aureus Map protein is an immunomodulator that interferes with T cell-mediated responses

The Staphylococcus aureus Map protein is an immunomodulator that interferes with T cell-mediated responses
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DOI:
10.1172/jc1200216318
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发表时间:
2002-11-01
影响因子:
15.9
通讯作者:
Brown, EL
Brown, EL
中科院分区:
医学1区
文献类型:
--
作者:
Lee, LY;Miyamoto, YJ;Brown, EL

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金黄色葡萄球菌 (SA) 是一种机会性病原体,影响多种器官系统,并导致世界范围内的许多疾病。 SA 表达 MHC II 类类似蛋白 (Map),它可能通过调节宿主免疫来增强 SA 的存活率。我们通过生成 Map 缺陷型 SA (Map-SA) 并将疾病结果与野生型 Map SA 感染小鼠进行比较,在小鼠中测试了这一假设。与对照动物相比,感染 Map-SA 的小鼠关节炎、骨髓炎和脓肿形成水平显着降低。此外,感染Map-SA的裸鼠出现关节炎和骨髓炎,其严重程度与感染Map(+)SA的对照组相似,这表明T细胞可以影响SA感染后的疾病结果,并且Map可能会减弱针对SA的细胞免疫。使用天然和重组形式的 Map 在体外和体内更具体地测试了 Map 改变 T 细胞功能的能力。 T细胞或用重组Map处理的小鼠分别具有减少的T细胞增殖反应和显着减少的针对攻击抗原的迟发型超敏反应。这些数据表明 Map 作为一种免疫调节蛋白,可能通过影响保护性细胞免疫在持续性 SA 感染中发挥作用。
Staphylococcus aureus (SA) is an opportunistic pathogen that affects a variety of organ systems and is responsible for many diseases worldwide. SA express an MHC class II analog protein (Map), which may potentiate SA survival by modulating host immunity. We tested this hypothesis in mice by generating Map-deficient SA (Map-SA) and comparing disease outcome to wild-type Map SA-infected mice. Map-SA-infected mice presented with significantly reduced levels of arthritis, osteomyelitis, and abscess formation compared with control animals. Furthermore, Map-SA-infected nude mice developed arthritis and osteomyelitis to a severity similar to Map(+)SA-infected controls, suggesting that T cells can affect disease outcome following SA infection and Map may attenuate cellular immunity against SA. The capacity of Map to alter T cell function was tested more specifically in vitro and in vivo using native and recombinant forms of Map. T cells or mice treated with recombinant Map had reduced T cell proliferative responses and a significantly reduced delayed-type hypersensitivity response to challenge antigen, respectively. These data suggest a role for Map as an immunomodulatory protein that may play a role in persistent SA infections by affecting protective cellular immunity.