| Project/Area Number |
13670252
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
寄生虫学(含医用動物学)
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| Research Institution | Miyazaki Medical College |
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Principal Investigator |
ISHIWATA Kenji Miyazaki Medical College, Dept. of Parasitol., Res. Associate, 医学部寄生虫学講座, 助手 (00241307)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Fukumi Miyazaki Medical College, Dept. of Parasitol., Res. Associate, 医学部寄生虫学講座, 助手 (90295204)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Mice / Parasite infection / Gastrointestinal nematode / Expulsion / Mucin / Sialic acid / International researcher exchange / United States of America |
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| Research Abstract |
The goal of our project is to get a better understanding on the protective mechanisms against gastrointestinal nematode infection. We employ Nippostrongylus brasiliensis-infected murine model that is one of the representative experimental models of gastrointestinal nematode infection. In this study, we firstly tried to interchange the information on protective mechanisms shown separately from rats- and mice-system. Expulsion mechanism in rats has been studied since 1930 and proposed to have two steps. Then we examined the two step theory in rats is also applicable in mice. Results suggested that first step, immune-mediated damage to the worms, is not essential for mice to expel adult N. brasiliensis from small intestine and that second step, non-specific mucosal responses, is critical (Ishiwata et al. 2002). Further, we suggested that the second step was Stat6-dependent goblet cell-response in mice. Both murine models have implied that CD4+ cells are important for the expulsion. Mice system recently showed the requirement of the IL-13/IL-4 receptor/Stat6 pathway for the adult N. brasiliensis expulsion. We next examined characteristic change in mice goblet cell mucins by lectin histochemistry. Results showed that sialic acid linkage in goblet cell mucin was associated with adult N. brasiliensis expulsion (Ishiwata et al. submitted). Furthermore, the expression of the enzyme, sialyltransferase, was upregulated at the time of worm expulsion or under exogenous IL-13 treatment which induces adult worm expulsion in scid mice. In summary, we suggested a protective mechanism against N. brasiliensis infection in mice as followed : CD4+ cells release IL-13 -> IL-13 binds to IL-4 receptor on goblet cells -> Stat6 activation -> up-regulation of the sialyltransferase expression -> sialic add linkage to mucin -> adult worm expulsion.
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