Dengue viruses and mononuclear phagocytes. II. Identity of blood and tissue leukocytes supporting in vitro infection.
Dengue viruses and mononuclear phagocytes. II. Identity of blood and tissue leukocytes supporting in vitro infection.
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DOI：
10.1084/jem.146.1.218
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发表时间：
1977-07-01
期刊：
影响因子：
--
通讯作者：
Allison AC
中科院分区：
文献类型：
--
作者：
Halstead SB;O'Rourke EJ;Allison AC
研究了人类和猴子单核白细胞对抗体增强的登革2型病毒（D2V）感染的认同。在分离后立即接种的外周血白细胞（PBL）培养物中，结论是只有单核吞噬细胞支持登革热感染。这是基于观察到d2v允许细胞可以抵抗1200拉德，具有塑料粘附性和非粘附性，当在10%胎牛血清或100%自体血清中通过尼龙羊毛柱时被去除，并通过100 μg/ml二氧化硅颗粒孵育被破坏。在直接免疫荧光染色中，24小时可见到核周登革热抗原，60小时达到最大值。含有抗原的细胞有丰富的细胞质，皱褶的细胞质膜，73%的细胞活跃吞噬。作为单核吞噬细胞感染的进一步证据，在5只恒河猴的骨髓培养物中观察到抗体增强的D2V复制，但在同一动物制备的脾脏、胸腺或淋巴结的细胞培养物中没有观察到。假设登革病毒与非中和抗体复合物通过免疫吞噬作用内化在单核吞噬细胞中，具有缺陷的病毒破坏机制。登革热容许性可能取决于细胞不成熟，因为骨髓白细胞即使在感染前保存4天也可能被感染，而PBL保存4天后容许性降低。体外单核吞噬细胞的抗体依赖感染应被证明是研究人登革热免疫病理机制的有用模型。
Studies were made on the identity of human and monkey mononuclear leukocytes permissive to antibody-enhanced dengue 2 virus (D2V) infection. In cultures of peripheral blood leukocytes (PBL) inoculated immediately after separation, it was concluded that only mononuclear phagocytes support dengue infection. This is based upon observations that D2V-permissive cells were resistant to 1,200 rads, were both plastic adherent and nonadherent, were removed when passed through nylon wool columns in 10 percent fetal bovine serum or 100 percent autologous serum, and were destroyed by incubation with 100 μg/ml particulate silica. On direct immunofluorescence staining, perinuclear dengue antigen was visualized at 24 h, becoming maximal at 60 h. Antigen-containing cells had ample cytoplasm, ruffled cytoplasmic membrane, and 73 percent were actively phagocytic. As further evidence of the infection of mononuclear phagocytes, antibody-enhanced D2V replication was observed in bone marrow cultures from five of five rhesus monkeys, but not in cell cultures of spleen, thymus, or lymph nodes prepared from the same animals. It is hypothesized that dengue virus complexed with non-neutralizing antibody is internalized by immune phagocytosis in a mononuclear phagocyte with a defective virus-destroying mechanism. Dengue permissiveness may depend upon cellular immaturity since bone marrow leukocytes could be infected even when held for 4 days before infection while PBL held for this time decreased in permissiveness. In vitro antibody-dependent infection of mononuclear phagocytes should prove useful as a model for study of immunopathologic mechanisms in human dengue.