NF-κB and inhibitor of apoptosis proteins are required for apoptosis resistance of epithelial cells persistently infected with Chlamydophila pneumoniae

Abstract

Infection with Chlamydophila pneumoniae (Cpn) renders host cells resistant to apoptosis induced by a variety of stimuli. While modulation of apoptosis has been extensively studied in cells acutely infected with Cpn, very little is known on how persistent chlamydial infection influences host cell survival. Here we show that epithelial cells persistently infected with Cpn resist apoptosis induced with TNFα or staurosporine. Cpn induced the activation of nuclear factor kappa B (NF-κB) and inhibition of NF-κB with a chemical inhibitor or by silencing expression of the p65 subunit sensitized infected cells for apoptosis induction by staurosporine or TNFα. Persistent infection resulted in the upregulation of the NF-κB regulated inhibitor of apoptosis protein 2 (cIAP-2) but not inhibitor of apoptosis protein 1 (cIAP-1). Interestingly, silencing of either cIAP-1 or cIAP-2 sensitized infected cells, suggesting that IAPs play an important role in the apoptosis resistance of persistently infected cells. © 2006 The Authors; Journal compilation © 2006 Blackwell Publishing Ltd.