[The role of mycobacterial secretory proteins in immune response in tuberculosis]

Data from recent studies indicate a complex role of Mycobacterium tuberculosis-specific secretory proteins such as MTSA-10 (10-kDa M. tuberculosis secretory antigen) and ESAT-6 (6-kDa early secretory antigenic target) in the immune response in tuberculosis. They can participate in development of protective immunity by activating macrophages, dendritic cells (DC), and mast cells to release proinflammatory mediators, tumor necrosis factor (TNF) and histamine, and by inducing differentiation and maturation of DCs that subsequently present mycobacterial antigens to T cells. These actions, in addition to immunodominance of MTSA- and ESAT-6-derived antigenic epitopes, may be involved in the protection obtained with the ESAT-6 or MTSA-10-containing vaccines. On the other hand, the proteins actively secreted by M. tuberculosis might be also partly responsible for mycobacterial evasion of the immune defense and complications of the ensuing disease in susceptible individuals. Mechanisms underlying the latter effect may include down-regulation of macrophage NO production and B7.1 expression, as well as impairment of DC capacity for optimal induction of Mtb-specific Th1 response. The immunomodulatory actions of MTSA-10 and ESAT-6 may contribute to survival of tuberculous bacilli in a susceptible host, as well as to delayed-type hypersensitivity reaction in diagnostic tests that employ these proteins. Therefore, a better understanding of immunomodulatory actions of M. tuberculosis-specific secretory proteins is a prerequisite for their possible exploitation in therapeutic and diagnostic purposes.