Induction of apoptosis and release of interleukin-1β by cell wall-associated 19-kDa lipoprotein during the course of mycobacterial infection

Antonio Ciaramella, Anna Cavone, Marilina B. Santucci, Sanjay K. Garg, Nunzia Sanarico, Marialuisa Bocchino, Domenico Galati, Angelo Martino, Giovanni Auricchio, Melania D'Orazio, Graham R. Stewart, Olivier Neyrolles, Douglas B. Young, Vittorio Colizzi, Maurizio Fraziano

Research output: Contribution to journalArticlepeer-review

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-Guérin (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-α. Only the release of interleukin (IL)-1β 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-1β during the early stages of mycobacterial infection.

Original languageEnglish
Pages (from-to)1167-1176
Number of pages10
JournalJournal of Infectious Diseases
Volume190
Issue number6
DOIs
Publication statusPublished - Sep 15 2004

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

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