Abstract
Mycobacterium tuberculosis induces apoptosis in human monocyte-derived macrophages (MDMs) during the early stages of infection. We investigated the proapoptotic role of cell wall-associated mycobacterial 19-kDa lipoprotein and the possible association between 19-kDa lipoprotein signaling and production of proinflammatory cytokines. Purified mycobacterial 19-kDa lipoprotein, 19-kDa lipoprotein-expressing M. smegmatis (M. smegmatis 19+), 19-kDa lipoprotein knockout (KO) M. tuberculosis, and 19-kDa lipoprotein KO M. bovis bacille Calmette-Guerin (BCG) strains were analyzed for their ability to induce apoptosis in MDMs. The 19-kDa lipoprotein and infection with M. smegmatis 19+ induced apoptosis in MDMs. M. tuberculosis and BCG KO strains had significantly decreased abilities to induce apoptosis. The 19-kDa lipoprotein proapoptotic signal was mediated by Toll-like receptor 2 but not by tumor necrosis factor-alpha. Only the release of interleukin (IL)-1 beta was decreased after infection with 19-kDa lipoprotein KO strains. These findings indicate that the 19-kDa lipoprotein is the main signal required to trigger both apoptosis and the release of IL-1 beta during the early stages of mycobacterial infection.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Annexin A5 / analysis
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Apoptosis*
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism*
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Cell Death
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Cell Nucleus / ultrastructure
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Cells, Cultured
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Cloning, Molecular
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Flow Cytometry
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Gene Deletion
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Humans
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Interleukin-1 / metabolism*
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L-Lactate Dehydrogenase / metabolism
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Macrophages / immunology
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Macrophages / microbiology*
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Macrophages / physiology*
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Membrane Glycoproteins / physiology
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Mycobacterium bovis / genetics
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Mycobacterium bovis / metabolism
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Mycobacterium smegmatis / genetics
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Mycobacterium smegmatis / metabolism
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Mycobacterium tuberculosis / genetics
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Mycobacterium tuberculosis / metabolism
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Mycobacterium tuberculosis / pathogenicity*
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Propidium / analysis
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Receptors, Cell Surface / physiology
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Signal Transduction
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Toll-Like Receptor 2
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Toll-Like Receptors
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Tumor Necrosis Factor-alpha / analysis
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Tumor Necrosis Factor-alpha / physiology
Substances
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19 kDa antigen, Mycobacterium
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Annexin A5
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Bacterial Proteins
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Interleukin-1
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Membrane Glycoproteins
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Receptors, Cell Surface
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Recombinant Proteins
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TLR2 protein, human
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Toll-Like Receptor 2
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Toll-Like Receptors
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Tumor Necrosis Factor-alpha
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Propidium
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L-Lactate Dehydrogenase