Gildea L A, Morris R E, Newman S L
Department of Internal Medicine, Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
J Immunol. 2001 Jan 15;166(2):1049-56. doi: 10.4049/jimmunol.166.2.1049.
Histoplasma capsulatum (Hc) is a facultative, intracellular parasite of world-wide importance. As the induction of cell-mediated immunity to Hc is of critical importance in host defense, we sought to determine whether dendritic cells (DC) could function as a primary APC for this pathogenic fungus. DC obtained by culture of human monocytes in the presence of GM-CSF and IL-4 phagocytosed Hc yeasts in a time-dependent manner. Upon ingestion, the intracellular growth of yeasts within DC was completely inhibited compared with rapid growth within human macrophages. Electron microscopy of DC with ingested Hc revealed that many of the yeasts were degraded as early as 2 h postingestion. In contrast to macrophages, human DC recognized Hc yeasts via the fibronectin receptor, very late Ag-5, and not via CD18 receptors. DC stimulated Hc-specific lymphocyte proliferation in a concentration-dependent manner after phagocytosis of viable and heat-killed Hc yeasts, but greater proliferation was achieved after ingestion of viable yeasts. These data demonstrate that human DC can phagocytose and degrade a fungal pathogen and subsequently process the appropriate Ags for stimulation of lymphocyte proliferation. In vivo, such interactions between DC and Hc may facilitate the induction of cell-mediated immunity.
荚膜组织胞浆菌（Hc）是一种具有全球重要性的兼性细胞内寄生虫。由于诱导针对Hc的细胞介导免疫在宿主防御中至关重要，我们试图确定树突状细胞（DC）是否可作为这种致病真菌的主要抗原呈递细胞。通过在GM-CSF和IL-4存在的情况下培养人单核细胞获得的DC以时间依赖性方式吞噬Hc酵母。摄入后，与在人巨噬细胞内的快速生长相比，DC内酵母的细胞内生长被完全抑制。对摄入Hc的DC进行电子显微镜检查显示，许多酵母早在摄入后2小时就被降解。与巨噬细胞不同，人DC通过纤连蛋白受体、极晚期抗原-5识别Hc酵母，而不是通过CD18受体。在吞噬活的和热灭活的Hc酵母后，DC以浓度依赖性方式刺激Hc特异性淋巴细胞增殖，但摄入活酵母后增殖更强。这些数据表明，人DC可以吞噬和降解真菌病原体，随后处理适当的抗原以刺激淋巴细胞增殖。在体内，DC与Hc之间的这种相互作用可能有助于诱导细胞介导免疫。
