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 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.
Hanekom
Willem A
WA
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
Mendillo
Megan
M
Manca
Claudia
C
Haslett
Patrick A J
PA
Siddiqui
M Ruby
MR
Barry
Clifton
C
Kaplan
Gilla
G
D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000382:microbiology*; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D007156:Immunologic Memory; D007375:Interleukin-1 / Q000494:pharmacology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000166:cytology* / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015415:Biomarkers; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone