Chlamydia pneumoniae and atherosclerosis: does the evidence support a causal or contributory role?

The intracellular bacterial pathogen Chlamydia pneumoniae causes respirator y tract infection and has: been associated with atherosclerosis and coronar y artery disease. Since atherosclerosis is a progressive disease and is con sidered to be a chronic inflammation of the artery vessel wall, the interac tion of C. pneumoniae with cells of the vasculature that can result in a lo cal inflammatory response is of paramount importance. In this essay we revi ew the pathophysiology of atherosclerosis in the context of C, pneumoniae i nfection and present an integrated model that includes the involvement of C . pneumoniae in all stages of atherogenesis including initiation, inflammat ion, fibrous plaque formation, plaque rupture and thrombosis. We hypothesiz e that acute and persistent infection of professional immune cells (T-cells . monocytes and macrophages) and non-immune cells (endothelial cells and sm ooth muscle cells) contributes to a sustained inflammatory response mediate d by extensive cellular 'crosstalk' acid numerous cytokines/chemokines. Thi s. cascade of inflammatory mediators may contribute to cellular dysfunction and tissue remodelling of the arterial intima. An improved understanding o f the precise mechanism(s) of C. pneumoniae involvement in atherogenesis ma y help resolve the question of causality however, at the present time. we i nterpret the data as favoring a contributory rather than a causal role. Fut ure research directed at the discovery of chlamydial virulence factors nece ssary for intracellular survival and subsequent alterations in host cell ge ne expression including signalling pathways may be important for the design of future clinical trials. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Microbiological Societies.