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

分枝杆菌疾病，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。世界上约有三分之一的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。结核病对全世界的健康构成重大威胁。分枝杆菌的致病性与它们逃避被摄入的巨噬细胞杀死、潜伏感染和诱导延迟型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arabinman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（包括鸟分枝杆菌复合体（MAC）的糖肽类磷脂（GPL）和分枝杆菌dna结合蛋白1 (MDP1)）反应的分子机制。在MAC疾病患者血清中检测到抗gpl抗体，而在结核病和接种卡介苗的健康人血清中未检测到抗gpl抗体（敏感性和特异性均大于或等于90%）。抗gpl抗体水平反映疾病活动性。GPL抗体的测定对MAC疾病的诊断和疾病活动性的评估都是有用的。MDP1参与分枝杆菌的缓慢生长和粘附/侵入宿主细胞。用MDP1- dna复合物处理小鼠后，宿主通过诱导干扰素-g和MDP1抗体来防御分枝杆菌感染。总的来说，分枝杆菌的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。更好地了解分枝杆菌感染的分子发病机制可能为开发治疗和预防干预措施开辟新的途径。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