Activation of natural killer T cells by α-galactosylceramide impairs DNA vaccine-induced protective immunity against Trypanosoma cruzi

Yasushi Miyahira, Masaharu Katae, Kazuyoshi Takeda, Hideo Yagita, Ko Okumura, Seiki Kobayashi, Tsutomu Takeuchi, Tsuneo Kamiyama, Yoshinosuke Fukuchi, Takashi Aoki

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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 α-galactosylceramide (α-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 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 T. cruzi infection. In addition, we found that the coadministration of α-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.

Original languageEnglish
Pages (from-to)1234-1241
Number of pages8
JournalInfection and Immunity
Volume71
Issue number3
DOIs
Publication statusPublished - 2003 Mar 1

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ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Miyahira, Y., Katae, M., Takeda, K., Yagita, H., Okumura, K., Kobayashi, S., Takeuchi, T., Kamiyama, T., Fukuchi, Y., & Aoki, T. (2003). Activation of natural killer T cells by α-galactosylceramide impairs DNA vaccine-induced protective immunity against Trypanosoma cruzi. Infection and Immunity, 71(3), 1234-1241. https://doi.org/10.1128/IAI.71.3.1234-1241.2003