Proinflammatory cytokines in the course of Mycobacterium tuberculosis-induced apoptosis in monocytes/macrophages

A. Ciaramella, A. Cavone, M. B. Santucci, M. Amicosante, A. Martino, G. Auricchio, L. P. Pucillo, V. Colizzi, M. Fraziano

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Abstract

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 MTB-induced 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.

Original languageEnglish
Pages (from-to)1277-1282
Number of pages6
JournalJournal of Infectious Diseases
Volume186
Issue number9
DOIs
Publication statusPublished - Nov 1 2002

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ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Ciaramella, A., Cavone, A., Santucci, M. B., Amicosante, M., Martino, A., Auricchio, G., Pucillo, L. P., Colizzi, V., & Fraziano, M. (2002). Proinflammatory cytokines in the course of Mycobacterium tuberculosis-induced apoptosis in monocytes/macrophages. Journal of Infectious Diseases, 186(9), 1277-1282. https://doi.org/10.1086/344645