The Journal of Experimental Medicine
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Published online 29 August 2005 doi:10.1084/jem.20042202
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 5, 607-616
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ARTICLE

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

Yuki Sasaki1,2, Tomohiro Yoshimoto1,2, Haruhiko Maruyama3, Tatsuya Tegoshi4, Nobuo Ohta3, Naoki Arizono4, and Kenji Nakanishi1,2

1 Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, 663-8501, Japan
2 Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama, 332-0012, Japan
3 Department of Medical Zoology, Nagoya City University Medical School, Nagoya, 467-8601, Japan
4 Department of Medical Zoology, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan

CORRESPONDENCE Kenji Nakanishi: nakaken{at}hyo-med.ac.jp

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 Strongyloides venezuelensis. In contrast, identically pretreated mast cell–deficient W/Wv 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.

Abbreviations used: MMC, mucosal mast cell; mMCP-1, mouse mast cell protease-1; L3, third-stage larvae; VCU, villous crypt units.


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