Bogdan C, Donhauser N, Döring R, Röllinghoff M, Diefenbach A, Rittig M G
Institute of Clinical Microbiology, Department of Anatomy, University of Erlangen, D-91054 Erlangen, Germany.
J Exp Med. 2000 Jun 19;191(12):2121-30. doi: 10.1084/jem.191.12.2121.
Intracellular parasites are known to persist lifelong in mammalian hosts after the clinical cure of the disease, but the mechanisms of persistence are poorly understood. Here, we show by confocal laser microscopy that in the draining lymph nodes of mice that had healed a cutaneous infection with Leishmania major, 40% of the persisting parasites were associated with fibroblasts forming the reticular meshwork of the lymph nodes. In vitro, both promastigotes and amastigotes of L. major infected primary skin or lymph node fibroblasts. Compared with macrophages, cytokine-activated fibroblasts had a reduced ability to express type 2 nitric oxide synthase and to kill intracellular L. major. These data identify fibroblasts as an important host cell for Leishmania during the chronic phase of infection and suggest that they might serve as safe targets for the parasites in clinically latent disease.
已知细胞内寄生虫在疾病临床治愈后会在哺乳动物宿主体内终生持续存在,但对其持续存在的机制了解甚少。在此,我们通过共聚焦激光显微镜显示,在已治愈皮肤利什曼原虫主要感染的小鼠引流淋巴结中,40% 的持续存在的寄生虫与形成淋巴结网状结构的成纤维细胞相关。在体外,利什曼原虫主要的前鞭毛体和无鞭毛体均可感染原代皮肤或淋巴结成纤维细胞。与巨噬细胞相比,细胞因子激活的成纤维细胞表达2型一氧化氮合酶和杀死细胞内利什曼原虫主要的能力降低。这些数据表明成纤维细胞是感染慢性期利什曼原虫的重要宿主细胞,并提示它们可能是临床潜伏疾病中寄生虫的安全靶点。