Survival ofChlamydia pneumoniae-Infected Mono Mac 6 Cells Is Dependent on NF-κB Binding Activity

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Abstract
The respiratory tract pathogenChlamydia pneumoniaehas been associated with atherosclerosis. Monocytes are supposed to serve as a vehicle for systemic dissemination of intracellularC. pneumoniaefrom the lung to the artery vessel wall. We were therefore interested in pathogen-induced cellular events associated with NF-κB, a crucial transcription factor for both inflammatory cytokines and antiapoptotic molecules. In this study we demonstrate by electrophoretic mobility shift assay thatC. pneumoniaeinfection of the human monocytic cell line Mono Mac 6 induces activation of NF-κB over 48 h, with a maximum level at 1 h postinfection. As shown by supershift assay, the activated NF-κB complex consists of the subunits RelA (p65) and NF-κB1 (p50). Apoptotic host cells were not detected during the early stages of the infection when maximal activation of NF-κB was detected. Pretreatment of Mono Mac 6 with the antioxidant and NF-κB inhibitor PDTC (pyrrolidine dithiocarbamate) induced activation of caspase-3 and led to apoptotic cell death. TheC. pneumoniae-induced activation of the NF-κB complex was reduced by PDTC, which in parallel resulted in an increased apoptosis, as quantified by annexin V labeling and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling reaction. In the complete absence of activated NF-κB, when Mono Mac 6 cells were pretreated with the more potent NF-κB inhibitors MG-132 and parthenolide aC. pneumoniae-mediated rescue of cells from induced apoptosis could not be achieved. Our results indicate that activation of NF-κB inC. pneumoniae-infected Mono Mac 6 cells is associated with protection of Mono Mac 6 cells against apoptosis and might thereby contribute to systemic spread of the pathogen.