Maisnier-Patin Karine, Malissard Martine, Jeannin Pascale, Haeuw Jean François, Corbière Jean-Claude, Hoeffel Guillaume, Gauchat Jean-François, Nguyen Thien, Saez José M, Delneste Yves
Centre d'Immunologie Pierre Fabre, 5 Avenue Napoléon III, 74160 Saint Julien en Genevois, France.
Vaccine. 2003 Sep 8;21(25-26):3765-74. doi: 10.1016/s0264-410x(03)00316-5.
Outer membrane proteins (OMP) are expressed in Gram-negative bacterial cell wall. OmpA from Klebsiella pneumoniae (KpOmpA) has been shown to bind and to activate selectively antigen presenting cells (APCs), eliciting protective CTL responses. In this study, we investigated whether OmpX, another member of the OMP family and structurally related to OmpA, exhibits the same immune properties. Using recombinant OmpX from Escherichia coli (EcOmpX), we report that EcOmpX binds to and is internalized by human APCs. However, EcOmpX does not activate APCs. EcOmpX acts as an efficient carrier protein as it induces a potent and Th1/Th2 mixed anti-TNP humoral response. However, adjuvant is required to generate a protective anti-tumoral immune response in mice injected with a tumor model antigen coupled to EcOmpX. Collectively, these data show that EcOmpX is recognized by innate cells but does not activate them, suggesting that EcOmpX does not provide a signal danger to APCs. In conclusion, this study provides information on the molecular mechanisms involved in the recognition and activation of innate cells by bacterial outer membrane proteins.
外膜蛋白（OMP）在革兰氏阴性菌细胞壁中表达。肺炎克雷伯菌的OmpA（KpOmpA）已被证明可结合并选择性激活抗原呈递细胞（APC），引发保护性CTL反应。在本研究中，我们调查了OMP家族的另一个成员且在结构上与OmpA相关的OmpX是否具有相同的免疫特性。使用来自大肠杆菌的重组OmpX（EcOmpX），我们报告EcOmpX可与人APC结合并被其内化。然而，EcOmpX不会激活APC。EcOmpX作为一种有效的载体蛋白，因为它可诱导强烈的Th1/Th2混合抗TNP体液反应。然而，在注射与EcOmpX偶联的肿瘤模型抗原的小鼠中，需要佐剂来产生保护性抗肿瘤免疫反应。总体而言，这些数据表明EcOmpX可被天然免疫细胞识别但不会激活它们，这表明EcOmpX不会向APC提供危险信号。总之，本研究提供了有关细菌外膜蛋白识别和激活天然免疫细胞所涉及分子机制的信息。
