Modelling Chlamydia infection of the cardiovascular system and the gastrointestinal tract

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Chlamydiae are ubiquitous obligate intracellular bacteria causing infection in the human eyes, urogenital and respiratory tract. Chlamydia pneumoniae (Cpn) a common respiratory pathogen has been implicated in the pathomechanism of several chronic non-infectious diseases. Association between atherosclerosis and Cpn infection has been investigated most thoroughly. Hyperlipidaemia model animals have been used to elucidate the role of Cpn infection in atherosclerosis. The aims of this study were to investigate the proatherogenic effect of multiple Cpn infections in ApoB100only/LDLR-/- mice which based on the lipid profile can be regarded as the most suitable mouse model of human hypercholesterolemia, and to compare the lesion development to that in a major atherosclerosis model ApoE-/- mice. Aorta samples of ApoB100only/LDLR-/- mice infected three times with Cpn were subjected to morphometric analyses. RT-PCR was used for searching for viable Cpn was detected in the ascending aorta. Morphometric evaluation disclosed that Cpn infections exacerbated atherosclerosis development in the aortic root and descending aorta of the mice fed with normal diet but further increase in response to Cpn infection was not observed in the mice kept on high fat-high cholesterol diet. Chlamydial 16SrRNA expression showed the presence of viable Cpn in the aorta of infected animals. A similar rate of acceleration of atherosclerosis was observed when the infection protocol was applied in ApoB100only/LDLR-/- and in ApoE-/- mice. In conclusion, similarly to ApoE-/- mice, ApoB100only/LDLR-/- mice with more human relevant serum lipoprotein composition, develop increased atherosclerosis after Cpn infections thus this mouse strain can be used as a model of infection-related atherosclerosis enhancement and provide further evidence for the proatherogenic influence of Cpn in mice. C. trachomatis causes infections of the eyes, urogenital and respiratory tracts. It is the most frequently identified sexually transmitted pathogen. Asymptomatic, repeat and chronic infections with C. trachomatis are common in the urogenital tract potentially causing severe reproductive pathology. Animal models of infection and epidemiological studies suggested the gastrointestinal tract as a reservoir of chlamydiae and as a source of repeat urogenital infections. Thus, we investigated the growth characteristics of C. trachomatis urogenital serovar D in human intestinal epithelial Caco-2 cells and the infection induced defensin production. Immunofluorescence staining and transmission electron microscopy showed the presence of chlamydial inclusions in the cells. Chlamydial DNA and viable C. trachomatis were recovered from Caco-2 cells in similar quantity compared to that detected in the usual in vitro host cell of this bacterium. The kinetics of expression of selected C. trachomatis genes in Caco-2 cells indicated prolonged replication with persisting high expression level of late genes and of heat shock protein gene groEL. Replication of C. trachomatis induced moderate level of β-defensin-2 production by Caco-2 cells, which might contribute to avoidance of immune recognition in the intestine. According to our results, Caco-2 cells support C. trachomatis replication, suggesting that the gastrointestinal tract is a site of residence for these bacteria.