Schaefer Martin, Reiling Norbert, Fessler Cornelia, Stephani Johannes, Taniuchi Ichiro, Hatam Farahnaz, Yildirim Ali Oender, Fehrenbach Heinz, Walter Kerstin, Ruland Juergen, Wagner Hermann, Ehlers Stefan, Sparwasser Tim
Institute for Medical Microbiology, Immunology, and Hygiene, Technische Universität München, Munich, Germany.
J Immunol. 2008 May 15;180(10):6836-45. doi: 10.4049/jimmunol.180.10.6836.
Dendritic cell (DC)-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN: CD209) is a C-type lectin that binds ICAM-2,3 and various pathogens such as HIV, helicobacter, and mycobacteria. It has been suggested that Mycobacterium tuberculosis, the causative agent of pulmonary tuberculosis, interacts with DC-SIGN to evade the immune system. To directly analyze the role of human DC-SIGN during mycobacterial infection, we generated conventional transgenic (tg) mice (termed "hSIGN") using CD209 cDNA under the control of the murine CD11c promoter. Upon mycobacterial infection, DCs from hSIGN mice produced significantly less IL-12p40 and no significant differences were be observed in the secretion levels of IL-10 relative to control DCs. After high dose aerosol infection with the strain M. tuberculosis H37Rv, hSIGN mice showed massive accumulation of DC-SIGN(+) cells in infected lungs, reduced tissue damage and prolonged survival. Based on our in vivo data, we propose that instead of favoring the immune evasion of mycobacteria, human DC-SIGN may have evolved as a pathogen receptor promoting protection by limiting tuberculosis-induced pathology.
树突状细胞（DC）特异性细胞间黏附分子3结合非整合素（DC-SIGN：CD209）是一种C型凝集素，可结合ICAM-2、3以及多种病原体，如HIV、幽门螺杆菌和分枝杆菌。有人提出，肺结核的病原体结核分枝杆菌与DC-SIGN相互作用以逃避免疫系统。为了直接分析人DC-SIGN在分枝杆菌感染过程中的作用，我们使用在小鼠CD11c启动子控制下的CD209 cDNA构建了传统转基因（tg）小鼠（称为“hSIGN”）。在分枝杆菌感染后，相对于对照DC，hSIGN小鼠的DC产生的IL-12p40明显减少，而IL-10的分泌水平未观察到显著差异。在用结核分枝杆菌H37Rv菌株进行高剂量气溶胶感染后，hSIGN小鼠感染的肺部出现大量DC-SIGN（+）细胞积聚，组织损伤减轻，存活时间延长。基于我们的体内数据，我们提出，人DC-SIGN可能并非促进结核分枝杆菌的免疫逃逸，而是作为一种病原体受体，通过限制结核病引起的病理变化来促进保护作用。
