TY - JOUR
T1 - Induction of apoptosis and release of interleukin-1β by cell wall-associated 19-kDa lipoprotein during the course of mycobacterial infection
AU - Ciaramella, Antonio
AU - Cavone, Anna
AU - Santucci, Marilina B.
AU - Garg, Sanjay K.
AU - Sanarico, Nunzia
AU - Bocchino, Marialuisa
AU - Galati, Domenico
AU - Martino, Angelo
AU - Auricchio, Giovanni
AU - D'Orazio, Melania
AU - Stewart, Graham R.
AU - Neyrolles, Olivier
AU - Young, Douglas B.
AU - Colizzi, Vittorio
AU - Fraziano, Maurizio
PY - 2004/9/15
Y1 - 2004/9/15
N2 - 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.
AB - 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.
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U2 - 10.1086/423850
DO - 10.1086/423850
M3 - Article
C2 - 15319868
AN - SCOPUS:4444377403
VL - 190
SP - 1167
EP - 1176
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 6
ER -