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Open Access Highly Accessed Research article

Serum lipoproteins attenuate macrophage activation and Toll-Like Receptor stimulation by bacterial lipoproteins

Sylvette Bas12*, Richard W James34 and Cem Gabay15

Author Affiliations

1 Division of Rheumatology, Department of Internal Medicine, Geneva University Hospital, 1211 Geneva 14, Switzerland

2 Division of Rheumatology, Department of Genetics and Laboratory Medicine, Geneva University Hospital, 1211 Geneva 14, Switzerland

3 Lipoprotein Research Group, Clinical Diabetes Unit, Department of Internal Medicine, Geneva University Hospital, Switzerland

4 Lipoprotein Research Group, Clinical Diabetes Unit, Department of Genetics and Laboratory Medicine, Geneva University Hospital, Switzerland

5 Division of Rheumatology, Department of Pathology and Immunology, Geneva University Hospital, Switzerland

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BMC Immunology 2010, 11:46  doi:10.1186/1471-2172-11-46

Published: 16 September 2010

Abstract

Background

Chlamydia trachomatis was previously shown to express a lipoprotein, the macrophage infectivity potentiator (Mip), exposed at the bacterial surface, and able to stimulate human primary monocytes/macrophages through Toll Like Receptor (TLR)2/TLR1/TLR6, and CD14. In PMA-differentiated THP-1 cells the proinflammatory activity of Mip was significantly higher in the absence than in the presence of serum. The present study aims to investigate the ability of different serum factors to attenuate Mip proinflammatory activity in PMA-differentiated THP-1 cells and in primary human differentiated macrophages. The study was also extend to another lipoprotein, the Borrelia burgdorferi outer surface protein (Osp)A. The proinflammatory activity was studied through Tumor Necrosis Factor alpha (TNF-α) and Interleukin (IL)-8 release. Finally, TLR1/2 human embryonic kidney-293 (HEK-293) transfected cells were used to test the ability of the serum factors to inhibit Mip and OspA proinflammatory activity.

Results

In the absence of any serum and in the presence of 10% delipidated FBS, production of Mip-induced TNF-α and IL-8 in PMA-differentiated THP-1 cells were similar whereas they were significantly decreased in the presence of 10% FBS suggesting an inhibiting role of lipids present in FBS. In the presence of 10% human serum, the concentrations of TNF-α and IL-8 were 2 to 5 times lower than in the presence of 10% FBS suggesting the presence of more potent inhibitor(s) in human serum than in FBS. Similar results were obtained in primary human differentiated macrophages. Different lipid components of human serum were then tested (total lipoproteins, HDL, LDL, VLDL, triglyceride emulsion, apolipoprotein (apo)A-I, B, E2, and E3). The most efficient inhibitors were LDL, VLDL, and apoB that reduced the mean concentration of TNF-α release in Mip-induced macrophages to 24, 20, and 2%, respectively (p < 0.0001). These lipid components were also able to prevent TLR1/2 induced activation by Mip, in HEK-293 transfected cells. Similar results were obtained with OspA.

Conclusions

These results demonstrated the ability of serum lipids to attenuate proinflammatory activity of bacterial lipoproteins and suggested that serum lipoproteins interact with acyl chains of the lipid part of bacterial lipoproteins to render it biologically inactive.