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

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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