IMMUNE RESPONSE TO GONOCOCCAL IRON-REGULATED PROTEINS

关于粘膜淋病引起的淋球菌抗原的免疫应答的数据很少。波士顿大学STD-CRC在阐明抗淋球菌免疫反应的某些方面起着中心作用。我们以前已经证明，急性淋病患者对淋球菌孔蛋白Por既有全身体液反应，又有循环T细胞反应。此外，我们已经证明，这种反应可能与预防淋球菌传播有关。我们希望通过研究淋病患者体内表达和对一组铁调节蛋白的免疫反应来扩展这些研究。这些蛋白包括1)铁结合蛋白A(FbpA)，一种存在于所有淋球菌中的铁的周质转运体；2)乳铁蛋白结合蛋白(LbpA)，从乳铁蛋白吸收铁所必需的；乳铁蛋白是泌尿生殖道粘膜(淋球菌的环境生态位)中含量最丰富的携铁蛋白；以及3)转铁蛋白结合蛋白A和B，它们是淋球菌从转铁蛋白吸收铁所必需的，目前正在作为潜在的候选疫苗进行研究，以预防淋球菌和脑膜炎球菌感染。淋球菌铁调节蛋白已被证明在淋病发病机制中发挥重要作用。例如，缺乏TbpA/B和LbpA的淋球菌不能在淋球菌性尿道炎的人类模型中引起感染。这项建议的具体目的是1)通过RT-PCR评估淋球菌铁调节基因在淋球菌感染患者急性获得的菌株中的表达，作为这些蛋白表达的指标，2)确定粘膜淋病患者对这些蛋白的抗体反应，3)确定粘膜淋病患者对这些蛋白的特异性T细胞反应，以及4)确定抗铁调节蛋白免疫反应是否与防止淋球菌感染的男性向女性传播有关。

There is a paucity of data regarding immune response to gonococcal antigens induced by mucosal gonococcal disease. The Boston University STD-CRC has been central in elucidating some aspects of the anti- gonococcal immune response. We have previously shown that patients with acute gonorrhea develop both a systemic humoral and a circulating T cell response towards the gonococcal porin, Por. In addition, we have demonstrated that this response might be associated with protection from gonococcal transmission. We wish to extend these studies by investigating the in vivo expression and the immune response in patients with gonorrhea to a group of iron regulated proteins. These include 1) ferric binding protein A (FbpA) a periplasmic transporter of iron that is present in all gonococci, 2) lactoferrin binding protein A (LbpA) required for uptake of iron from lactoferrin, which is the most abundant iron carrying protein in the urogenital mucosa (the environmental niche of the gonococcus) and 3) transferrin binding proteins A and B which are necessary for gonococcal iron uptake from transferrin and are currently being investigated as potential vaccine candidates to prevent both gonococcal and meningococcal infections. Gonococcal iron regulated proteins have been demonstrated to play an essential role in gonococcal pathogenesis. For example,, gonococci that lacks TbpA/B and LbpA are unable to cause an infection in a human model of gonococcal urethritis. The specific aims of this proposal are 1) to assess the expression of the gonococcal iron-regulated genes by RT-PCR in gonococcal strains acutely obtained from patients with gonococcal infection as an indicator of expression of these proteins, 2) determine the antibody response towards these proteins in patients with mucosal gonococcal disease, 3) determine the specific T cell response towards these proteins in patients with mucosal gonococcal disease and 4) determine if the anti-iron regulated protein immune response can be correlated to prevention of male to female transmission of gonococcal infection.