Activation of natural killer T cells by alpha-galactosylceramide impairs DNA vaccine-induced protective immunity against Trypanosoma cruzi |
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Authors: | Miyahira Yasushi Katae Masaharu Takeda Kazuyoshi Yagita Hideo Okumura Ko Kobayashi Seiki Takeuchi Tsutomu Kamiyama Tsuneo Fukuchi Yoshinosuke Aoki Takashi |
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Affiliation: | Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan. miyahira@med.juntendo.ac.jp |
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Abstract: | 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 Trypanosoma cruzi infection. The T. cruzi parasitemia and survival of CD1d-deficient mice exhibited no differences compared to wild-type littermates. NK T-cell activation induced by administering alpha-galactosylceramide (alpha-GalCer) to T. cruzi-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 alpha-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 T. cruzi infection. In addition, we found that the coadministration of alpha-GalCer with DNA vaccine impaired the induction of epitope-specific CD8(+) T cells and undermined the DNA vaccine-induced protective immunity against T. cruzi. 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. |
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