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]-α, interleukin [IL]-1β, and prostaglandin E₂ [PGE₂]), 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-α, IL-1β, and PGE₂. 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.