Mycobacterium tuberculosis inhibits maturation of human monocyte-derived dendritic cells in vitro

To induce effector immunity, dendritic cells (DCs) must differentiate into fully mature cells. We show that, after human monocyte-derived DCs were infected with virulent Mycobacterium tuberculosis, up-regulation of cellular-surface maturation markers was minimal and reversible. In the presence of a potent stimulus for maturation (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, and prostaglandin E-2 [PGE(2)]), M. tuberculosis inhibited phenotypic DC maturation. M. tuberculosis - infected DCs had an impaired ability to induce allogeneic lymphoproliferation and activated autologous memory CD4(+) and CD8(+) T cells optimally only in the presence of TNF-alpha, IL-1beta, and PGE(2). Thus, virulent M. tuberculosis inhibits phenotypic and functional maturation of human monocyte-derived DCs. This mechanism, which has been described elsewhere for various viruses and for the virulent mycobacterium M. leprae, may be a novel mechanism that this pathogen uses to evade the host's immune response.