Interferon-γ-activated primary enterocytes inhibit Toxoplasma gondii replication:: a role for intracellular iron
Interferon-γ-activated primary enterocytes inhibit Toxoplasma gondii replication:: a role for intracellular iron
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DOI：
10.1046/j.1365-2567.1998.00553.x
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发表时间：
1998-08-01
期刊：
影响因子：
6.4
通讯作者：
Bout, DT
中科院分区：
文献类型：
--
作者：
Dimier, IH;Bout, DT
刚地弓形虫是一种专性细胞内寄生虫，在包括人在内的众多中间宿主中感染多种有核细胞。经口途径是弓形虫的天然入口。被摄入的微生物从胃肠道内的囊肿或卵囊中释放出来，最初侵入肠上皮。我们发现弓形虫在培养的原代大鼠肠细胞中侵入并增殖，这些细胞是用原始程序获得的。用大鼠重组干扰素γ (ifn - γ)激活肠细胞可抑制弓形虫的复制，这种抑制作用是剂量依赖性的。无论是氮和氧衍生物还是色氨酸饥饿似乎都没有参与ifn - γ对寄生虫复制的抑制。使用Fe2+盐、载体和螯合剂的实验表明，细胞内弓形虫的复制依赖于铁，这表明ifn - γ处理的肠细胞通过限制细胞内铁对寄生虫的可用性来抑制弓形虫的复制。我们的数据表明，肠细胞可能在粘膜表面发挥主要作用，通过免疫机制作为抵抗这种球虫和其他病原体的第一道防线。结果表明，限制铁的可用性可能代表了一种广泛的抗菌机制，通过该机制，激活的肠细胞对细胞内病原体施加控制。
Toxoplasma gondii is an obligate intracellular parasite that infects a wide variety of nucleated cells in its numerous intermediate hosts including man. The oral route is the natural portal of entry of T. gondii. Ingested organisms are released from cysts or oocysts within the gastrointestinal tract and initially invade the intestinal epithelium. We show that T. gondii invades and proliferates in cultured primary rat enterocytes, obtained with an original procedure. Activation of the enterocytes with rat recombinant interferon-gamma (IFN-gamma) inhibits T. gondii replication, the inhibition being dose dependent. Neither nitrogen and oxygen derivatives nor tryptophan starvation appear to be involved in the inhibition of parasite replication by IFN-gamma. Experiments using Fe2+ salt, carrier and chelator indicate that intracellular T gondii replication is iron dependent, suggesting that IFN-gamma-treated enterocytes inhibit T. gondii replication by limiting the availability of intracellular iron to the parasite. Our data show that enterocytes probably play a major role on mucosal surfaces as a first line of defence against this coccidia, and possibly other pathogens, through an immune mechanism. The results suggest that limiting the availability of iron could represent a broad antimicrobial mechanism through which the activated enterocytes exert control over intracellular pathogens.