Induction of apoptosis and release of interleukin-1 beta by cell wall-associated 19-kDa lipoprotein during the course of mycobacterial infection.
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.
Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, Italy.
Antonio
A
Ciaramella
Anna
A
Cavone
Marilina B
MB
Santucci
Sanjay K
SK
Garg
Nunzia
N
Sanarico
Marialuisa
M
Bocchino
Domenico
D
Galati
Angelo
A
Martino
Giovanni
G
Auricchio
Melania
M
D'Orazio
Graham R
GR
Stewart
Olivier
O
Neyrolles
Douglas B
DB
Young
Vittorio
V
Colizzi
Maurizio
M
Fraziano
D017304:Annexin A5 / Q000032:analysis; D017209:Apoptosis; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death; D002467:Cell Nucleus / Q000648:ultrastructure; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005434:Flow Cytometry; D017353:Gene Deletion; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000382:microbiology* / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology; D009163:Mycobacterium bovis / Q000235:genetics / Q000378:metabolism; D020102:Mycobacterium smegmatis / Q000235:genetics / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D011419:Propidium / Q000032:analysis; D011956:Receptors, Cell Surface / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000502:physiology
C087864:19 kDa antigen, Mycobacterium; D017304:Annexin A5; D001426:Bacterial Proteins; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D011419:Propidium; D007770:L-Lactate Dehydrogenase