IL-18 with IL-2 protects against Strongyloides venezuelensis infection by activating mucosal mast cell-dependent type 2 innate immunity.
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/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-18Ralpha(-/-) 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-18Ralpha(-/-) 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.
Sasaki
Yuki
Y
Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Japan.
Yoshimoto
Tomohiro
T
Maruyama
Haruhiko
H
Tegoshi
Tatsuya
T
Ohta
Nobuo
N
Arizono
Naoki
N
Nakanishi
Kenji
K
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D006652:Histological Techniques; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D050800:STAT6 Transcription Factor / Q000235:genetics; D013321:Strongyloides / Q000276:immunology*; D013322:Strongyloidiasis / Q000276:immunology* / Q000517:prevention & control*
D020382:Interleukin-18; D007376:Interleukin-2; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse