The molecular mechanism of host responses against cell wall components of mycobacteria

分枝杆菌病，包括结核病、麻风病和由非结核分枝杆菌引起的疾病，是全世界传染病死亡的主要原因。约三分之一的世界人口潜伏感染结核分枝杆菌。每年有800多万新病例和近200万人死亡。结核病对全世界构成重大健康威胁。分枝杆菌的致病性与其逃避被摄入的巨噬细胞杀死、潜伏感染和诱导迟发型超敏反应的能力有关。这归因于分枝杆菌细胞壁的几种组分，如表面糖脂、脂阿拉伯甘露聚糖、补体激活因子、热休克蛋白和分枝杆菌DNA结合蛋白。本论文主要研究了分枝杆菌复合体（MAC）的糖肽脂（GPL）和分枝杆菌属（Mc）的糖肽脂（GPL）等细胞壁组分对宿主免疫应答的分子机制 ...更多信息 细胞DNA结合蛋白1（MDP 1）。血清抗GPL抗体在MAC疾病患者中检测到，但在结核病和接种BCG的健康个体中未检测到（灵敏度和特异性[大于或等于] 90%）。抗GPL抗体水平反映疾病活动性。抗GPL抗体的测定对MAC病的诊断和病情活动性的评估均有一定的意义。MDP 1参与分枝杆菌缓慢生长和粘附/侵入宿主细胞。用MDP 1-DNA复合物处理小鼠，通过诱导宿主中的干扰素-g和MDP 1抗体，导致宿主对分枝杆菌感染的防御。总的来说，分枝杆菌的表面分子在微生物和宿主中发挥多效性活性，从而参与分枝杆菌疾病的发病机制。对分枝杆菌感染的分子发病机制的深入了解可能为治疗和预防干预的发展开辟新的途径。少

Mycobacterial diseases, including tuberculosis, leprosy, and disease due to nontuberculous mycobacteria, are the major cause of death from infectious diseases around the world. About one-third of the world population is latently infected with Mycobacterium tuberculosis. Over 8 million new cases and nearly 2 million deaths occur each year. Tuberculosis presents a significant health threat to the world. The pathogenicity of mycobacteria is related to their ability to escape killing by ingested macrophages, latent infection, and induce delayed-type hypersensitivity. This has been attributed to several components of the mycobacterial cell wall, such as surface glycolipids, lipoarabinomannan, complement activation factor, heat-shock protein, and mycobacterial DNA-binding protein. In the present study, we have focused on the molecular mechanism of host responses against cell wall components of mycobacteria, including glycopeptidolipid (GPL) of Mycobacterium avium complex (MAC) and mycobacter … More ial DNA-binding protein 1 (MDP1). Serum anti-GPL antibody was detected in patients with MAC diseases, but not in tuberculosis and healthy individuals vaccinated with BCG (sensitivity and specificity 【greater than or equal】 90%). The levels of anti-GPL antibody reflected disease activity. The measurement of antibody to GPL is useful for both diagnosis of MAC disease and assessment of diseases activity. MDP1 participates in both slow growth and adhesion/invasion of mycobacteria into host cells. Treatment of mice with MDP1-DNA complex resulted in host defense against mycobacterial infection by the induction of interferon-g and antibody to MDP1 in the host. Collectively, surface molecules of mycobacteria exert pleiotropic activities in both the microbe and host, and thus participate in the pathogenesis of mycobacterial diseases. The better understanding of molecular pathogenesis in mycobacterial infection may open the new avenue for the development of therapeutic and prophylactic interventions. Less