TUMOR-NECROSIS-FACTOR-ALPHA RESTORES GRANULOMAS AND INDUCES PARASITE EGG-LAYING IN SCHISTOSOME-INFECTED SCID MICE
TUMOR-NECROSIS-FACTOR-ALPHA RESTORES GRANULOMAS AND INDUCES PARASITE EGG-LAYING IN SCHISTOSOME-INFECTED SCID MICE
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DOI：
10.1038/356604a0
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发表时间：
1992-04-16
期刊：
影响因子：
64.8
通讯作者：
MCKERROW, JH
中科院分区：
文献类型：
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作者：
AMIRI, P;LOCKSLEY, RM;MCKERROW, JH
血吸虫病（裂体血吸虫病）是一种由几种血蠕虫（血吸虫）引起的寄生虫病。这种疾病的关键致病事件是在肝门静脉中捕获的虫卵周围形成肉芽肿1-9。肉芽肿是一种独特形式的慢性炎症，其特征在于激活的巨噬细胞在激发刺激周围局部聚集10。每一个肉芽肿都会演变成纤维性瘢痕;在血吸虫病中，结果是广泛的肝纤维化和门静脉高压。为了鉴定肉芽肿形成所需的特异性免疫信号分子，我们研究了严重联合免疫缺陷（SCID）小鼠的巨噬细胞感染，这些小鼠具有正常的巨噬细胞，但缺乏功能性B或T淋巴细胞11，12。在这里，我们报告说，免疫调节细胞因子肿瘤坏死因子-α是必要的，足以重建肉芽肿的形成，在cystosome感染的SCID小鼠。此外，我们发现，寄生蠕虫需要肿瘤坏死因子-α产卵和排泄的鸡蛋从主机。后一个结果的含义是，寄生虫已经成功地适应了它的宿主，它使用宿主衍生的免疫调节蛋白作为复制和传播的信号。
SCHISTOSOMIASIS (bilharzia) is a parasitic disease caused by several species of schistosome worms (blood flukes). The key pathogenic event in this disease is the formation of granulomas around schistosome eggs trapped in portal venules of the liver 1-9. Granulomas are a distinctive form of chronic inflammation characterized by localized aggregation of activated macrophages around an inciting stimulus 10. Each granuloma evolves to form a fibrous scar; in schistosomiasis, the result is widespread hepatic fibrosis and portal hypertension. To identify the specific immune signal molecules necessary for granuloma formation, we studied schistosome infections in severe combined immunodeficient (SCID) mice, which have normal macrophages but lack functional B or T lymphocytes 11,12. Here we report that the immunoregulatory cytokine tumour necrosis factor-alpha is necessary and sufficient to reconstitute granuloma formation in schistosome-infected SCID mice. Moreover, we find that the parasitic worms require tumour necrosis factor-alpha for egg-laying and for excretion of eggs from the host. The implication of this latter result is that the parasite has adapted so successfully to its host that it uses a host-derived immunoregulatory protein as a signal for replication and transmission.