Division of Pathology, US Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, USA.
Immunotherapy. 2009 Mar;1(2):187-97. doi: 10.2217/1750743X.1.2.187.
Viral hemorrhagic fevers (VHFs) often cause high mortality with high infectivity, multiorgan failure, shock and hemorrhagic diathesis. Fibroblastic reticular cells (FRCs) within secondary lymphoid organs provide a supporting scaffold to T-lymphocyte areas. These cells regulate the movement of various immune cells and soluble molecules that promote T-lymphocyte homeostasis. We previously reported Ebola virus infection of FRCs, but ascribed little significance to this finding. Here, we studied infection of FRCs by Ebola, Marburg and Lassa viruses. We demonstrate that FRCs, or the extracellular 'conduit' of the fibroblastic reticulum of nonhuman primates, are targets of Ebola, Marburg and Lassa viruses. Furthermore, we observed that FRC damage correlates temporally and spatially with lymphocyte damage and that FRCs serve as nidi of fibrin deposition. In addition, we show that nonhuman primate FRCs express p75 NGF receptor and tissue transglutaminase. Our data suggest that viral infection of FRCs may be crucial to the immunological dysfunction and coagulopathy characteristic of VHFs. We further propose that p75 NGF receptor and tissue transglutaminase may be involved in FRC-associated dysfunction during the course of infection.
病毒性出血热（VHF）通常具有高传染性、多器官衰竭、休克和出血素质，导致高死亡率。次级淋巴器官中的纤维母细胞网状细胞（FRC）为 T 淋巴细胞区域提供了支持性支架。这些细胞调节各种免疫细胞和促进 T 淋巴细胞稳态的可溶性分子的运动。我们之前报道了埃博拉病毒感染 FRC，但认为这一发现意义不大。在这里，我们研究了埃博拉、马尔堡和拉萨病毒对 FRC 的感染。我们证明 FRC 或非人类灵长类动物纤维母细胞网状纤维的细胞外“导管”是埃博拉、马尔堡和拉萨病毒的靶标。此外，我们观察到 FRC 损伤与淋巴细胞损伤在时间和空间上相关，并且 FRC 充当纤维蛋白沉积的灶。此外，我们还表明，非人类灵长类动物 FRC 表达 p75NGF 受体和组织转谷氨酰胺酶。我们的数据表明，FRC 的病毒感染可能是 VHF 免疫功能障碍和凝血功能障碍的关键。我们进一步提出，p75NGF 受体和组织转谷氨酰胺酶可能参与感染过程中与 FRC 相关的功能障碍。
