Mycobacterium tuberculosis inhibits maturation of human monocyte-derived dendritic cells in vitro |
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Authors: | Hanekom Willem A Mendillo Megan Manca Claudia Haslett Patrick A J Siddiqui M Ruby Barry Clifton Kaplan Gilla |
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Affiliation: | Department of Pediatrics, Division of Infectious Disease and Immunology, University of Miami School of Medicine, 1550 NW 10th Avenue, Suite 211 (D4-4), Miami, FL 33136, USA. whanekom@med.miami.edu |
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Abstract: | 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 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-alpha, IL-1beta, 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. |
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