Porphyromonas gingivalis modulates Pseudomonas aeruginosa-induced apoptosis of respiratory epithelial cells through the STAT3 signaling pathway

Periodontitis: from microbial immune subversion to systemic inflammation

“…Polymicrobial infections including the opportunistic pathogen Pseudomonas aeruginosa are associated with exacerbations of COPD increasing its morbidity and mortality 23,146 . P. gingivalis is readily detected with P. aeruginosa in tracheal aspirates of patients with acute COPD exacerbations 24 and can enhance the pathogenicity of P. aeruginosa in the context of lower airway infection 147,148 . Indeed, P. gingivalis promotes the ability of P. aeruginosa to invade respiratory epithelial cells and modulates its apoptosis-inducing capacity 147,148 .…”

“…P. gingivalis is readily detected with P. aeruginosa in tracheal aspirates of patients with acute COPD exacerbations 24 and can enhance the pathogenicity of P. aeruginosa in the context of lower airway infection 147,148 . Indeed, P. gingivalis promotes the ability of P. aeruginosa to invade respiratory epithelial cells and modulates its apoptosis-inducing capacity 147,148 . Specifically, compared with P. aeruginosa invasion alone, co-invasion of respiratory epithelial cells with both bacteria leads to diminished apoptosis as a result of enhanced signal transducer and activator of transcription 3 (STAT3) signalling, which upregulates the expression of the anti-apoptotic molecules survivin and B cell lymphoma 2 (BCL-2), in turn leading to caspase 3 inhibition 148 .…”

“…Indeed, P. gingivalis promotes the ability of P. aeruginosa to invade respiratory epithelial cells and modulates its apoptosis-inducing capacity 147,148 . Specifically, compared with P. aeruginosa invasion alone, co-invasion of respiratory epithelial cells with both bacteria leads to diminished apoptosis as a result of enhanced signal transducer and activator of transcription 3 (STAT3) signalling, which upregulates the expression of the anti-apoptotic molecules survivin and B cell lymphoma 2 (BCL-2), in turn leading to caspase 3 inhibition 148 . Moreover, co-invasion is followed by downregulation of the pro-apoptotic molecule BCL-2-associated agonist of cell death (BAD) 148 , possibly mediated by phosphoinositide 3-kinase (PI3K)–AKT signalling 149 (see Figure in BOX 2 ).…”

“…Specifically, compared with P. aeruginosa invasion alone, co-invasion of respiratory epithelial cells with both bacteria leads to diminished apoptosis as a result of enhanced signal transducer and activator of transcription 3 (STAT3) signalling, which upregulates the expression of the anti-apoptotic molecules survivin and B cell lymphoma 2 (BCL-2), in turn leading to caspase 3 inhibition 148 . Moreover, co-invasion is followed by downregulation of the pro-apoptotic molecule BCL-2-associated agonist of cell death (BAD) 148 , possibly mediated by phosphoinositide 3-kinase (PI3K)–AKT signalling 149 (see Figure in BOX 2 ). However, the inhibition of apoptosis is transient since the signalling pathways involved start to decline 8 hours post-invasion of both bacteria, leading to dramatically increased caspase-3 activity by 12 hours post-invasion 148 .…”

“…Moreover, co-invasion is followed by downregulation of the pro-apoptotic molecule BCL-2-associated agonist of cell death (BAD) 148 , possibly mediated by phosphoinositide 3-kinase (PI3K)–AKT signalling 149 (see Figure in BOX 2 ). However, the inhibition of apoptosis is transient since the signalling pathways involved start to decline 8 hours post-invasion of both bacteria, leading to dramatically increased caspase-3 activity by 12 hours post-invasion 148 . Rapid apoptosis of infected epithelial cells is thought to contribute to effective clearance of P. aeruginosa 150 .…”