Pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial DNA
Research output: Contribution to journal › Article
Colleges, School and Institutes
- Department of Internal Medicine/Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
- Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117, Berlin, Germany.
- Department of Pneumology and Department of Thoracic Surgery, HELIOS Clinic Emil von Behring, Walterhöferstr 11, 14165, Berlin, Germany.
- Department for General and Thoracic Surgery, DRK Clinics, Drontheimer Strasse 39-40, 13359, Berlin, Germany.
- Department of General, Visceral, Vascular and Thoracic Surgery, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
- Department of Thoracic Surgery, Vivantes Clinics Neukölln, Rudower Straße 48, 12351, Berlin, Germany.
- Department of Internal Medicine/Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. firstname.lastname@example.org.
Streptococcus pneumoniae (S.pn.) is the most common bacterial pathogen causing community acquired pneumonia. The pore-forming toxin pneumolysin (PLY) is the major virulence factor of S.pn. and supposed to affect alveolar epithelial cells thereby activating the immune system by liberation of danger-associated molecular patterns (DAMP). To test this hypothesis, we established a novel live-cell imaging based assay to analyse mitochondrial function and associated release of mitochondrial DNA (mtDNA) as DAMP in real-time. We first revealed that bacterially released PLY caused significant changes of the cellular ATP homeostasis and led to morphologic alterations of mitochondria in human alveolar epithelial cells in vitro and, by use of spectral live-tissue imaging, in human alveoli. This was accompanied by strong mitochondrial calcium influx and loss of mitochondrial membrane potential resulting in opening of the mitochondrial permeability transition pore and mtDNA release without activation of intrinsic apoptosis. Moreover, our data indicate cellular mtDNA liberation via microvesicles, which may contribute to S.pn. related pro-inflammatory immune activation in the human alveolar compartment.
|Publication status||Published - 9 Jan 2018|
- Cell death and immune response, Cellular microbiology, Infection