Borrelia burgdorferi downregulates ICAM-1 on human synovial cells in vitro

Lyme arthritis following infection with Borrelia burgdorferi (B. burgdorfer i) is associated with the presence of bacteria in the joint, but the mechan ism of persistent infection in the presence of specific antibodies and lymp hocytes remains unknown. To investigate how an infection with B. burgdorfer i might influence the local immune response in the joint, we examined the e xpression of cell adhesion molecules, human leucocyte antigens and inducibl e nitric oxide synthase (iNOS)-1 and -2 in human synovial cells after infec tion with B. burgdorferi in vitro. Synovial cells are known to influence th e function of local immunologic effector cells and play a key role in the p annus formation of erosive arthritis. It has been shown previously that B. burgdorferi can persist in the cytosol of human synovial cells. The express ion of the surface molecules ICAM-1, VCAM-1, HLA-class-I and -class-II and the cytosolic production of iNOS-1 and -2 in synovial cells was measured by flow cytometry for up to 5 days after infection with B. burgdorferi. A sig nificant, lasting downregulation of surface ICAM-1 could be demonstrated on synovial cells, whereas no significant changes were seen in the expression of VCAM-1, HLA-class-I and -II, and of iNOS-1 and -2. To determine the bio logical significance of this downregulation an in vitro adhesion assay usin g peripheral blood mononuclear cells was developed. After infection with B. burgdorferi a significantly smaller number of mononuclear cells was adheri ng to the synovial cell monolayer. Adhesion of peripheral mononuclear cells was shown to be in part mediated by ICAM-1 by using a blocking mononuclear antibody against ICAM-1. Downregulation of ICAM-1 on synovial cells due to infection with B. burgdorferi might suppress the local immunosurveillance and might help the bacteria to persist in joint cells in vivo.