The chlamydiae are important obligate intracellular prokaryotic pathogens that, each year, are responsible for millions of human infections involving the eye, genital tract, respiratory tract, vasculature and joints. The chlamydiae grow in cytoplasmic vesicles in susceptible host cells, which include the mucosal epithelium, vascular endothelium, smooth muscle cells, circulating monocytes and recruited or tissue-specific macrophages. One important pathogenic strategy that chlamydiae have evolved to promote their survival is the modulation of programmed cell death pathways in infected host cells. The chlamydiae can elicit the induction of host cell death, or apoptosis, under some circumstances and actively inhibit apoptosis under others. This subtle pathogenic mechanism highlights the manner in which these highly successful pathogens take control of infected cells to promote their own survival — even under the most adverse circumstances.
The chlamydiae are important obligate intracellular prokaryotic pathogens that replicate in cytoplasmic vesicles in a variety of different eukaryotic host cells, including the mucosal and vascular epithelia, smooth muscle cells, monocytes and macrophages.
A key pathogenic strategy of the chlamydiae is the ability to induce host-cell apoptosis under some circumstances and actively inhibit apoptosis under others. This flexible strategy is crucial for the pathogenic success of the chlamydiae as these organisms cause diseases in many different species and in many different host cell types, and a pro-apoptotic response in one host species or cell might not be appropriate in another host species or cell type. Also, the intracellular growth cycle of the chlamydiae is complex and can be productive or non-productive under different growth conditions and the growth status of the bacteria might affect their apoptotic activity.
Chlamydia-mediated protection against apoptosis occurs via a variety of different mechanisms. It is thought that Chlamydia trachomatis and Chlamydia pneumoniae can protect infected cells by inhibiting the release of cytochrome c from mitochondria. These chlamydial species also upregulate the expression of the anti-apoptotic mediators IAP and MCL-1. C. pneumoniae infection of monocytes also activates the transcription of NF-κB, although how this transcription factor contributes to the inhibition of apoptosis is still unclear. Protection against apoptosis may be a strategy that the chlamydiae use to maintain a persistent, chronic infection.
Chlamydia induction of host cell death has been a recognised phenomenon for more than 30 years, but the mechanisms of this cytotoxicity have only recently begun to be explored. Again, it is likely that different chlamydial species or biovars use different mechanisms and that the same species could use different mechanisms in different host species or cell types. Recent studies have shown that this apoptosis may be caspase independent. A chlamydial protein known as CADD — Chlamydia protein associating with death receptors — was recently identified and it has been suggested that CADD inhibits Fas-mediated apoptosis or induces cell death under different conditions.
Read more at: https://www.nature.com/articles/nrmicro1007