Inhibition of apoptosis in neuronal cells infected with Chlamydophila (Chlamydia) pneumoniae

SK-N-MC neuroblastoma cells were infected with the respiratory strain of C. pneumoniae, AR39 at an MOI of 1. Following infection, the cells were either untreated or treated with staurosporine and then examined for apoptosis by labeling for nuclear fragmentation, caspase activity, and membrane inversion as indicated by annexin V staining. C. pneumoniae infection was maintained through 10 days post-infection. At 3 and 10 days post-infection, the infected cell cultures appeared to inhibit or were resistant to the apoptotic process when induced by staurosporine. This inhibition was demonstrated quantitatively by nuclear profile counts and caspase 3/7 activity measurements.These data suggest that C. pneumoniae can sustain a chronic infection in neuronal cells by interfering with apoptosis, which may contribute to chronic inflammation in the AD brain.The mechanisms and morphological changes that underlie the apoptotic process leading to cell death have been well-described [1,2]. In this regard, the induction of apoptosis has been shown to be important in embryonic development and in defending against infection of a eukaryotic host by microorganisms. Examples of the latter have been shown for both viral and bacterial infections [3,4]. In contrast, some organisms, such as the intracellular pathogen Chlamydia pneumoniae, have the capacity to inhibit the apoptotic process following infection [5-7]. This inhibition has been demonstrated in a number of different cell types, including neutrophils [8], monocytes [9,10], epithelial cells [10-12], and microglial cells [13]. Some Chlamydia-infected host cells are resistant to pro-apoptotic stimuli such as TNFα, Fas antibody, staurosporine, and UV-light [6,14], and C. pneumoniae infection has been shown to down regulate pro-apoptotic cytoplasmic proteins such as caspase-3 and cytochrome c. Intriguingly, C. pneumoniae infection also has been shown to activate anti-apoptotic proteins such as Bcl-2 and NF-κβ [15], the latter of which is