REDUCED REPLICATION OF TOXOPLASMA-GONDII IS NECESSARY FOR INDUCTION OF BRADYZOITE-SPECIFIC ANTIGENS - A POSSIBLE ROLE FOR NITRIC-OXIDE IN TRIGGERING STAGE CONVERSION
REDUCED REPLICATION OF TOXOPLASMA-GONDII IS NECESSARY FOR INDUCTION OF BRADYZOITE-SPECIFIC ANTIGENS - A POSSIBLE ROLE FOR NITRIC-OXIDE IN TRIGGERING STAGE CONVERSION
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DOI：
10.1128/iai.62.5.1761-1767.1994
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发表时间：
1994-05-01
影响因子：
3.1
通讯作者：
GROSS, U
中科院分区：
文献类型：
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作者：
BOHNE, W;HEESEMANN, J;GROSS, U
以小鼠骨髓来源的巨噬细胞(BMMS)为宿主细胞，研究了弓形虫慢速殖子与速殖子之间的体外阶段转换。在未经处理的BMMS感染速殖子后，缓殖子特异性抗原(BSA)的自发表达频率较低，弓形虫株依赖率为0.03~2%。如前所述，对于腹膜巨噬细胞，感染速殖子的骨髓基质细胞用干扰素或脂多糖激活后可诱导牛血清白蛋白的产生。当慢殖子用于感染时，在干扰素-γ激活的骨髓基质细胞中可观察到BSA的持续表达。BSA表达的诱导似乎与寄生虫的增殖密切相关，在中等激活的巨噬细胞中，BSA表达的最大值增加到50%到70%，其中一氧化氮(NO)水平允许减少寄生虫的复制。用硝普钠作为外源NO的来源时，阶段转化的结果相同，表明NO可能是阶段转化的分子触发因素。NO与蛋白质中的铁硫中心发生反应，从而抑制参与线粒体呼吸链的蛋白质。使用寡霉素和抗霉素A作为线粒体功能的抑制剂，获得了抑制寄生虫生长和诱导牛血清白蛋白的作用。由于小胶质细胞是中枢神经系统巨噬细胞的功能相关细胞，并在干扰素-γ激活时抑制弓形虫，因此在脑囊肿发育过程中可能涉及类似的机制。
Stage conversion between tachyzoites and bradyzoites of Toxoplasma gondii was investigated in vitro by using murine bone marrow-derived macrophages (BMMs) as host cells. Following infection of untreated BMMs with tachyzoites, spontaneous expression of bradyzoite-specific antigens (Bsa) occurred at low frequency with Toxoplasma strain-dependent ratios from 0.03 to 2%. As previously described for peritoneal macrophages, activation of tachyzoite-infected BMMs with gamma interferon (IFN-gamma) or lipopolysaccharide resulted in the induction of Bsa. When bradyzoites were used for infection, prolonged expression of Bsa could be observed in IFN-gamma-activated BMMs. The induction of Bsa expression seemed to be closely linked to parasite multiplication and increased to maximal values of 50 to 70% in intermediately activated macrophages with nitric oxide (NO) levels that allowed reduced parasite replication. Identical results in stage conversion were obtained when sodium nitroprusside was used as a source of exogenous NO, indicating that NO might be a molecular trigger of stage conversion. NO is reactive with iron-sulfur centers in proteins, thereby inhibiting proteins involved in the mitochondrial respiratory chain. Using oligomycin and antimycin A as inhibitors of mitochondrial function, growth inhibition of parasites and induction of Bsa were obtained. Since microglia are the functional correlates of macrophages in the central nervous system and inhibit T. gondii upon activation with IFN-gamma, a similar mechanism might be involved during cyst development in the brain.