Journal Article

Mycobacterium tuberculosis Inhibits Maturation of Human Monocyte-Derived Dendritic Cells In Vitro

Mendillo, Megan, Haslett, Patrick A. J., Barry, Clifton, Hanekom, Willem A., Manca, Claudia, Siddiqui, M. Ruby, Kaplan, Gilla

2003

Overview

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. tuberculosisinhibits 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.

• Publisher: The University of Chicago Press,University of Chicago Press,Oxford University Press
• Subject: Bacteria / Bacteriology / Biological and medical sciences / Biomarkers / Cell Differentiation - drug effects / Cell Survival / Cocktails / Cytokines / Cytometry / Dendritic cells / Dendritic Cells - cytology / Dendritic Cells - drug effects / Dendritic Cells - microbiology / Dinoprostone - pharmacology / Fundamental and applied biological sciences. Psychology / Humans / Immunity / Immunologic Memory / Infections / Interleukin-1 - pharmacology / Lymphocyte Activation / Microbiology / Monocytes - cytology / Monocytes - microbiology / Mycobacterium tuberculosis / Mycobacterium tuberculosis - physiology / Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains / Phenotype / Phenotypes / T lymphocytes / T-Lymphocytes - immunology / Tuberculosis / Tumor Necrosis Factor-alpha - pharmacology