IL-18 with IL-2 protects against Strongyloides venezuelensis infection by activating mucosal mast cell-dependent type 2 innate immunity
IL-18 with IL-2 protects against Strongyloides venezuelensis infection by activating mucosal mast cell-dependent type 2 innate immunity
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DOI：
10.1084/jem.20042202
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发表时间：
2005-09-05
影响因子：
15.3
通讯作者：
Nakanishi, K
中科院分区：
文献类型：
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作者：
Sasaki, Y;Yoshimoto, T;Nakanishi, K
用 IL-18 加 IL-2 预处理的 C57BL/6 (B6) 和 B6 背景 STAT6(-/-) 小鼠表现出显着的肠道肥大细胞增多症，并快速排出胃肠道线虫委内瑞拉 Stronyyloides 成虫。相比之下，经过同样预处理的肥大细胞缺陷型 W/W-v 小鼠却未能做到这一点。因此，激活的粘膜肥大细胞（MMC）对于寄生虫的排出至关重要。感染委内瑞拉沙门氏菌第三期幼虫（L3）的B6小鼠在感染后第12天完成寄生虫排出，而IL-18（-/-）或IL-18Rα（-/-）B6小鼠在寄生虫排出方面表现出明显的损害，表明IL-18依赖性MMC激活对寄生虫排出有重大贡献。与IL-18(-/-)或IL-18R α(-/-)小鼠相比，S. venezuelensis L3感染的STAT6(-/-)小鼠MMC活化较差且持续感染；尽管他们的 IL-18 产生是正常的。 IL-18 和 IL-2 的中和进一步减少了受感染 STAT6(-/-) 小鼠的排出。这些结果表明 IL-18 依赖性肥大细胞增多症和 Th2 细胞依赖性肥大细胞增多症之间的协作对于迅速驱除寄生虫非常重要。
C57BL/6 (B6) and B6 background STAT6(-/-) mice pretreated with IL-18 plus IL-2 showed prominent intestinal mastocytosis and rapidly expelled implanted adult worms of the gastrointestinal nematode Stronyyloides venezuelensis. In contrast, identically pretreated mast cell-deficient W/W-v mice failed to do so. Thus, activated mucosal mast cells (MMC) are crucial for parasite expulsion. B6 mice infected with S. venezuelensis third-stage larvae (L3) completed parasite expulsion by day 12 after infection, whereas IL-18(-/-) or IL-18R alpha(-/-) B6 mice exhibited marked impairment in parasite expulsion, suggesting a substantial contribution of IL-18-dependent MMC activation to parasite expulsion. Compared with IL-18(-/-) or IL-18R alpha(-/-) mice, S. venezuelensis L3-infected STAT6(-/-) mice have poorly activated MMC and sustained infection; although their IL-18 production is normal. Neutralization of IL-18 and IL-2 further reduces expulsion in infected STAT6(-/-) mice. These results suggest that collaboration between IL-18-dependent and Th2 cell-dependent mastocytosis is important for prompt parasite expulsion.