Activation of Natural Killer T Cells by α-Galactosylceramide Impairs DNA Vaccine-Induced Protective Immunity against<i>Trypanosoma cruzi</i>
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- Yasushi Miyahira
- Department of Molecular and Cellular Parasitology
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- Masaharu Katae
- Department of Molecular and Cellular Parasitology
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- Kazuyoshi Takeda
- Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421
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- Hideo Yagita
- Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421
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- Ko Okumura
- Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421
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- Seiki Kobayashi
- Department of Tropical Medicine and Parasitology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582
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- Tsutomu Takeuchi
- Department of Tropical Medicine and Parasitology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582
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- Tsuneo Kamiyama
- Department of Veterinary Sciences, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan
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- Yoshinosuke Fukuchi
- Department of Respiratory Medicine
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- Takashi Aoki
- Department of Molecular and Cellular Parasitology
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<jats:title>ABSTRACT</jats:title><jats:p>Innate immunity as a first defense is indispensable for host survival against infectious agents. We examined the roles of natural killer (NK) T cells in defense against<jats:italic>Trypanosoma cruzi</jats:italic>infection. The<jats:italic>T. cruzi</jats:italic>parasitemia and survival of CD1d-deficient mice exhibited no differences compared to wild-type littermates. NK T-cell activation induced by administering α-galactosylceramide (α-GalCer) to<jats:italic>T. cruzi</jats:italic>-infected mice significantly changed the parasitemia only in the late phase of infection and slightly improved survival when mice were infected intraperitoneally. The combined usage of α-GalCer and benznidazole, a commercially available drug for Chagas' disease, did not enhance the therapeutic efficacy of benznidazole. These results suggest that NK T cells do not play a pivotal role in resistance to<jats:italic>T. cruzi</jats:italic>infection. In addition, we found that the coadministration of α-GalCer with DNA vaccine impaired the induction of epitope-specific CD8<jats:sup>+</jats:sup>T cells and undermined the DNA vaccine-induced protective immunity against<jats:italic>T. cruzi</jats:italic>. Our results, in contrast to previous reports demonstrating the protective roles of NK T cells against other infectious agents, suggest that these cells might even exhibit adverse effects on vaccine-mediated protective immunity.</jats:p>
収録刊行物
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- Infection and Immunity
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Infection and Immunity 71 (3), 1234-1241, 2003-03
American Society for Microbiology
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詳細情報 詳細情報について
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- CRID
- 1360011145801186560
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- NII論文ID
- 30020830888
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- NII書誌ID
- AA00673732
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- ISSN
- 10985522
- 00199567
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