McCaskill Joshua G, Chason Kelly D, Hua Xiaoyang, Neuringer Isabel P, Ghio Andrew J, Funkhouser William K, Tilley Stephen L
Department of Medicine, Division of Pulmonary Diseases and Cricital Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7219, USA.
Am J Respir Cell Mol Biol. 2006 Sep;35(3):347-56. doi: 10.1165/rcmb.2005-0285OC. Epub 2006 Apr 27.
Propionibacterium acnes (PA) is a gram-positive anaerobic bacterium implicated as a putative etiologic agent of sarcoidosis. To characterize the pulmonary immune response to PA, C57BL/6 and BALB/c mice were intraperitoneally sensitized and intratracheally challenged with heat-killed bacteria. C57BL/6 mice challenged with PA developed a cellular immune response characterized by elevations in Th1 cytokines/chemokines, increased numbers of lymphocytes and macrophages in lung lavage fluid, and peribronchovascular granulomatous inflammation composed of T- and B-lymphocytes and epithelioid histiocytes. T-lymphocytes in the lung lavage fluid showed a marked CD4+ cell predominance. In contrast, C57BL/6 mice challenged with Staphylococcus epidermidis (SE), another gram-positive commensal of human skin, and BALB/c mice challenged with PA, showed only a modest induction of Th1 cytokines, less pulmonary inflammation, and no granulomatous changes in the lung. Enhancement of Toll-like receptor expression was seen in PA-exposed C57BL/6 mice within 24 h after exposure, suggesting that induction of innate immunity by PA contributes to the robust, polarized Th1 immune response elicited by this bacterium. These findings suggest that PA-induced pulmonary inflammation may be a useful model for testing the contributions of both bacterial and host factors in the development, maintenance, and resolution of granulomatous inflammation in the lung.
痤疮丙酸杆菌(PA)是一种革兰氏阳性厌氧菌,被认为是结节病的潜在病原体。为了表征肺部对PA的免疫反应,对C57BL/6和BALB/c小鼠进行腹腔致敏,并经气管内给予热灭活细菌进行攻击。用PA攻击的C57BL/6小鼠产生了细胞免疫反应,其特征为Th1细胞因子/趋化因子升高、肺灌洗液中淋巴细胞和巨噬细胞数量增加,以及由T淋巴细胞、B淋巴细胞和上皮样组织细胞组成的支气管血管周围肉芽肿性炎症。肺灌洗液中的T淋巴细胞显示出明显的CD4+细胞优势。相比之下,用表皮葡萄球菌(SE,人类皮肤的另一种革兰氏阳性共生菌)攻击的C57BL/6小鼠,以及用PA攻击的BALB/c小鼠,仅表现出适度的Th1细胞因子诱导、较少的肺部炎症,且肺部无肉芽肿性变化。在暴露于PA的C57BL/6小鼠中,暴露后24小时内可见Toll样受体表达增强,这表明PA诱导的固有免疫有助于该细菌引发的强大、极化的Th1免疫反应。这些发现表明,PA诱导的肺部炎症可能是一个有用的模型,用于测试细菌和宿主因素在肺部肉芽肿性炎症的发生、维持和消退中的作用。