IL-18 with IL-2 protects against Strongyloides venezuelensis infection by activating mucosal mast cell-dependent type 2 innate immunity

被引:81
作者
Sasaki, Y
Yoshimoto, T
Maruyama, H
Tegoshi, T
Ohta, N
Arizono, N
Nakanishi, K [1 ]
机构
[1] Hyogo Med Univ, Dept Immunol & Med Zool, Nishinomiya, Hyogo 6638501, Japan
[2] Nagoya City Univ, Sch Med, Dept Med Zool, Nagoya, Aichi 4678601, Japan
[3] Kyoto Prefectural Univ Med, Dept Med Zool, Kyoto 6028566, Japan
关键词
D O I
10.1084/jem.20042202
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:607 / 616
页数:10
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