Proinflammatory Cytokines in the Course of "Mycobacterium Tuberculosis"-Induced Apoptosis in Monocytes/Macrophages

Mycobacterium tuberculosis (MTB) can induce apoptosis in monocytes/macrophages both in vitro and in vivo, and this phenomenon is associated with mycobacterial survival. The present study addresses the possibility that apoptotic and inflammatory pathways could coexist through a caspase-1-mediated mec...

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Bibliographic Details
Published in:The Journal of infectious diseases 2002-11, Vol.186 (9), p.1277-1282
Main Authors: Ciaramella, A., Cavone, A., Santucci, M. B., Amicosante, M., Martino, A., Auricchio, G., Pucillo, L. P., Colizzi, V., Fraziano, M.
Format: Article
Language:English
Subjects:
Annexins
Apoptosis
Apoptosis - drug effects
Apoptosis - physiology
Bacterial diseases
Biological and medical sciences
Cell Survival - drug effects
Cells, Cultured
Cysteine Proteinase Inhibitors - pharmacology
Cytokines
Cytokines - biosynthesis
Enzyme Inhibitors - pharmacology
Human bacterial diseases
Humans
In Vitro Techniques
Infections
Infectious diseases
Lipoproteins
Macrophages
Macrophages - cytology
Macrophages - immunology
Macrophages - microbiology
Major Articles
Medical sciences
Monocytes
Monocytes - cytology
Monocytes - immunology
Monocytes - microbiology
Mycobacterium tuberculosis
Mycobacterium tuberculosis - immunology
Pretreatment
T lymphocytes
Tuberculosis and atypical mycobacterial infections
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Summary:Mycobacterium tuberculosis (MTB) can induce apoptosis in monocytes/macrophages both in vitro and in vivo, and this phenomenon is associated with mycobacterial survival. The present study addresses the possibility that apoptotic and inflammatory pathways could coexist through a caspase-1-mediated mechanism. In this context, a caspase-1 inhibitor (YVAD), but not caspase-3 (DEVD) or caspase-4 (LEVD) inhibitors, was able to strongly inhibit MTBinduced apoptosis. Moreover, caspase-1 activity was confirmed by the increased maturation of interleukin (IL)-1β. Of interest, IL-1β and tumor necrosis factor (TNF)-α were produced massively in the course of infection, and both were inhibited by YVAD pretreatment. To determine whether TNF-α was produced actively by apoptotic cells, the intracytoplasmatic cytokine content and apoptotic phenotype were analyzed at the single-cell level. Results showed a progressive increase of TNF-α production in annexin V-positive cells. These results indicate that MTB-induced apoptosis is associated with proinflammatory cytokine production.
ISSN:0022-1899
1537-6613
DOI:10.1086/344645