TAK 21d although the source of infection remains unclear, infection has been associated with environmental exposure. In particular, M. mesophilicum contamination of hospital tap water has been implicated as the source of an isolated nosocomial outbreak. Previous studies have demonstrated that TLR2 and TLR4 are the most abundant TLRs in human atherosclerotic lesions. TLR2 mediates host responses to bacteria principally by recognition of the lipopeptides, and TLR4 mediates host responses to bacteria by recognition of LPS. In the current study we demonstrated that although M. oryzae does not activate TLR4 signalling and stimulates only mild TLR2 signalling, this bacterium can trigger an aggressive macrophage-mediated pro-inflammatory response that may potentiate atherosclerosis. It has been suggested that RA patients exhibit a distinctive oral enterotype, characterised by the overabundance of a single and virulent Porphyromonas species. It can be speculated that a reduction in oral bacterial heterogeneity may reduce the diversity of microbes entering the bloodstream. Furthermore, RA is characterised by a chronic systemic T-cell response and increased expression of pro-inflammatory mediators and cytokines such as TNF-a, IL-17 and IL-1. This may explain the reduction in bacterial heterogeneity in the adventitia of RA+CVD patients observed in the present study. Conceivably, the increased systemic inflammatory state associated with RA may reduce the ability of certain bacteria to invade the body and enter systemic circulation, although this remains to be established. Also, anti-rheumatic treatment may contribute to an imbalance in the immune system, resulting in the different bacterial populations observed between RA+CVD and CVD patients. Complement C2-deficient individuals have a high frequency of severe infections and systemic lupus erythematosus-like disorders. Interestingly they also have a very high frequency of CVD, as has been shown for RA patients in our current study. Although our current study is relatively small, it is still important as no similar studies have been performed earlier and, due to feasibility, studies on surgical SDZ NKT 343 vascular specimens in RA are often lacking or small. In conclusion, our study suggests that bacterial colonisation of the aortic adventitia might contribute to the development of atherosclerotic disease.