Grab D J, Lanners H, Martin L N, Chesney J, Cai C, Adkisson H D, Bucala R
Tulane Regional Primate Research Center, Covington, Louisiana, USA.
Mol Med. 1999 Jan;5(1):46-54.
Borrelia Burgdorferi has a predilection for collagenous tissue and can interact with fibronectin and cellular collagens. While the molecular mechanisms of how B. burgdorferi targets connective tissues and causes arthritis are not understood, the spirochetes can bind to a number of different cell types, including fibroblasts. A novel circulating fibroblast-like cell called the peripheral blood fibrocyte has recently been described. Fibrocytes express collagen types I and III as well as fibronectin. Besides playing a role in wound healing, fibrocytes have the potential to target to connective tissue and the functional capacity to recruit, activate, and present antigen to CD4(+) T cells.
Rhesus monkey fibrocytes were isolated and characterized by flow cytometry. B. burgdorferi were incubated with human or monkey fibrocyte cultures in vitro and the cellular interactions analyzed by light and electron microscopy. The two strains of B. burgdorferi studied included JD1, which is highly pathogenic for monkeys, and M297, which lacks the cell surface OspA and OspB proteins.
In this study, we demonstrate that B. burgdorferi binds to both human and monkey (rhesus) fibrocytes in vitro. This process does not require OspA or OspB. In addition, the spirochetes are not phagocytosed but are taken into deep recesses of the cell membrane, a process that may protect them from the immune system.
This interaction between B. burgdorferi and peripheral blood fibrocytes provides a potential explanation for the targeting of spirochetes to joint connective tissue and may contribute to the inflammatory process in Lyme arthritis.
伯氏疏螺旋体对胶原组织有偏好,并且能够与纤连蛋白和细胞胶原相互作用。虽然目前尚不清楚伯氏疏螺旋体靶向结缔组织并引发关节炎的分子机制,但这种螺旋体可与多种不同细胞类型结合,包括成纤维细胞。最近描述了一种名为外周血纤维细胞的新型循环成纤维细胞样细胞。纤维细胞表达I型和III型胶原以及纤连蛋白。除了在伤口愈合中发挥作用外,纤维细胞还具有靶向结缔组织的潜力以及募集、激活并向CD4(+) T细胞呈递抗原的功能能力。
分离恒河猴纤维细胞并通过流式细胞术进行表征。将伯氏疏螺旋体与人类或猴纤维细胞培养物在体外孵育,并通过光学显微镜和电子显微镜分析细胞间相互作用。所研究的两株伯氏疏螺旋体包括对猴具有高度致病性的JD1以及缺乏细胞表面OspA和OspB蛋白的M297。
在本研究中,我们证明伯氏疏螺旋体在体外可与人及猴(恒河猴)纤维细胞结合。该过程不需要OspA或OspB。此外,螺旋体不会被吞噬,而是被摄入细胞膜的深层凹陷处,这一过程可能使其免受免疫系统攻击。
伯氏疏螺旋体与外周血纤维细胞之间的这种相互作用为螺旋体靶向关节结缔组织提供了一种潜在解释,并且可能有助于莱姆关节炎的炎症过程。