The protective roles of IL-18 in host defense against gastro-intestinal nematode infection by in duction of Th2 responses.

IL-18能增强IL-12诱导的Th1免疫应答，但在缺乏IL-12的情况下也能刺激Th2免疫应答。在这里，我们发现IL-18加IL-2处理小鼠可诱导Th2细胞因子(IL-3、IL-4、IL-9和IL-13)、肠粘膜肥大细胞(MMC)和MMC特异性的小鼠肥大细胞蛋白酶-1(mMCP-1)的释放，从而极快地驱逐胃肠道线虫成虫。这种诱导依赖于CD4+T细胞，而不是STAT6。野生型小鼠感染沙门氏菌L3后血清IL-18水平显著升高。此外，当IL-18-/-小鼠感染文氏链霉菌L3时，与野生型小鼠相比，驱虫显著延迟。这些发现证实了IL-18通过诱导功能性肠道MMC对胃肠道线虫的免疫作用。

IL-18 enhances the IL-12-deriven Th1 immune responses, but it can also stimulate Th2 immune response in the absence of IL-12. Here we show that IL-18 plus IL-2 treatment of mice induces Th2 cytokines(IL-3,IL-4,IL-9 and IL-13), intestinal mucosal mast cells(MMC) and the release of MMC-specific mouse mast cell protease-1(mMCP-1), resulting in extremely rapid expulsion of adult worms of gastrointestinal nematode Strongyloides venezuelensis(S.venezuelensis). This induction is dependent on CD4+ T cells, but not on stat6. Wild-type mice infected with S.venezuelensis L3 significantly increase in serum levels of IL-18. Furthermore, when IL-18-/-mice are infected with S.venezuelensis L3, worm expulsion is significantly delayed as compared with wild-type mice. These findings establish a role for IL-18 in immunity to gastrointestinal nematode by induction of functional intestinal MMC.