Houngbédji Mabèrou Germain, Boissinot Maurice, Bergeron G Michel, Frenette Jérôme
Centre Hospitalier Universitaire de Québec - Centre de Recherche du Centre Hospitalier de l'Université Laval (CHUQ-CRCHUL), 2705 boulevard Laurier, T-R-93 Québec, QC, G1V 4G2, Canada.
Microbes Infect. 2008 Oct;10(12-13):1236-43. doi: 10.1016/j.micinf.2008.07.041. Epub 2008 Aug 13.
Mycobacterium ulcerans (M. ulcerans) causes Buruli ulcer, a very debilitating disease that affects the skin and other tissues. The disease occurs mainly in children in sub-Sahara Africa. While contracture, fibrosis and functional limitation of range of motion are frequent complications of Buruli ulcer, no fundamental or clinical studies have investigated the impact of M. ulcerans infections on skeletal muscle. In the present study, we subcutaneously infected mice in the proximity of the right biceps muscle to evaluate the histological, biochemical and functional impact of M. ulcerans on skeletal muscles. The concentration of mast cells decreased but the number of neutrophils and macrophages increased steadily in proximate-infected biceps muscles. Pro- and anti-inflammatory cytokines as well as fibrogenic growth factor mRNA also increased. Significantly more membrane damage and fibrosis occurred in proximate-infected biceps muscles than in control and sham muscles. Passive biomechanical testing also revealed that the presence of M. ulcerans increased muscle stiffness. These findings show for the first time that M. ulcerans can induce local and chronic inflammatory responses in skeletal muscles that are associated with muscle fiber damage and fibrosis.
溃疡分枝杆菌可引发布氏溃疡，这是一种严重影响皮肤及其他组织的致残性疾病。该疾病主要发生在撒哈拉以南非洲地区的儿童中。虽然挛缩、纤维化以及活动范围的功能受限是布氏溃疡常见的并发症，但尚无基础或临床研究探究溃疡分枝杆菌感染对骨骼肌的影响。在本研究中，我们在小鼠右肱二头肌附近进行皮下感染，以评估溃疡分枝杆菌对骨骼肌的组织学、生化及功能影响。在临近感染的肱二头肌中，肥大细胞浓度降低，但中性粒细胞和巨噬细胞数量稳步增加。促炎和抗炎细胞因子以及促纤维化生长因子mRNA也有所增加。与对照肌肉和假手术肌肉相比，临近感染的肱二头肌出现了明显更多的膜损伤和纤维化。被动生物力学测试还显示，溃疡分枝杆菌的存在会增加肌肉僵硬程度。这些发现首次表明，溃疡分枝杆菌可在骨骼肌中诱导局部和慢性炎症反应，这些反应与肌纤维损伤和纤维化相关。
