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

分枝杆菌病，包括结核病、麻风病和非结核分枝杆菌引起的疾病，是世界各地传染病死亡的主要原因。世界上约三分之一的人口潜伏着感染结核分枝杆菌。每年新增病例超过800万例，死亡近200万例。结核病对世界构成重大的健康威胁。分枝杆菌的致病性与其逃避吞噬巨噬细胞的杀伤、潜伏感染和诱导迟发性超敏反应的能力有关。这归因于分枝杆菌细胞壁的几种成分，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。在本研究中，我们重点研究了宿主对分枝杆菌细胞壁成分的反应的分子机制，包括禽型分枝杆菌复合体的糖肽脂(Gpl)和分枝杆菌…。更多的al DNA结合蛋白1(MDP1)。血清抗GPL抗体在MAC疾病患者中检测到，而在结核病和接种卡介苗的健康人中检测不到(敏感性和特异性[大于或等于]90%)。抗GPL抗体水平反映了疾病的活动性。GPL抗体的检测对MAC病的诊断和疾病活动性的评估均有一定的参考价值。MDP1参与了分枝杆菌的缓慢生长和对宿主细胞的黏附/入侵。用MDP1-DNA复合体处理小鼠，通过诱导宿主产生干扰素-g和MDP1抗体，从而产生对分枝杆菌感染的宿主防御。总的来说，分枝杆菌表面分子在微生物和宿主中都发挥着多效性，从而参与了分枝杆菌疾病的发病机制。深入了解分枝杆菌感染的分子发病机制，可能为治疗和预防措施的发展开辟新的途径。较少

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