Streptococcus pneumoniae-induced caspase 6-dependent apoptosis in lung epithelium.
Streptococcus pneumoniae is the major pathogen of community-acquired pneumonia and one of the most common causes of death due to infectious diseases in industrialized countries. Lung epithelium lines the airways and constitutes the first line of innate defense against respiratory pathogens. Little is known about the molecular interaction of pneumococci with lung epithelial cells. Apoptosis of lung epithelium is involved in some bacterial lung infections. In this study different pneumococcal strains specifically induced either apoptotic or necrotic death of human alveolar and bronchial epithelial cells. Pneumococcus-induced apoptosis did not depend on the virulence factors pneumolysin and H(2)O(2). Apoptotic cells showed increased activity of caspases 6, 8, and 9 but not increased activity of caspase 3. Moreover, programmed cell death could be strongly reduced by a caspase 6 inhibitor and a pan-caspase inhibitor. Inhibitors of calpain and chymotrypsin- and trypsin-like proteases also reduced pneumococcus-induced apoptosis. Furthermore, pneumococcus-infected human alveolar epithelial cells showed Bid cleavage and reduced levels of Bcl2 and Bax. Overexpression of Bcl2 in these cells reduced apoptosis significantly. Thus, pneumococci induced apoptosis of human alveolar and bronchial epithelial cells. Programmed cell death was executed by caspase 6 and noncaspase proteases, but not by caspase 3, and could be blocked by overexpression of Bcl2.
Department of Internal Medicine/Infectious Diseases Charité-University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
Bernd
B
Schmeck
Ralph
R
Gross
Phillipe Dje
PD
N'Guessan
Andreas C
AC
Hocke
Sven
S
Hammerschmidt
Tim J
TJ
Mitchell
Simone
S
Rosseau
Norbert
N
Suttorp
Stefan
S
Hippenstiel
D017209:Apoptosis; D001980:Bronchi / Q000166:cytology* / Q000382:microbiology; D053178:Caspase 6; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000382:microbiology / Q000473:pathology*; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000472:pathogenicity*
D019253:Proto-Oncogene Proteins c-bcl-2; C505514:CASP6 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053178:Caspase 6; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases