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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Galactosylceramides
Natural Killer T-Cells
DNA Vaccines
Trypanosoma cruzi
Immunity
Parasitemia
Infection
Chagas Disease
Innate Immunity
Epitopes
Vaccines
T-Lymphocytes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Immunology

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Activation of natural killer T cells by α-galactosylceramide impairs DNA vaccine-induced protective immunity against Trypanosoma cruzi. / Miyahira, Yasushi; Katae, Masaharu; Takeda, Kazuyoshi; Yagita, Hideo; Okumura, Ko; Kobayashi, Seiki; Takeuchi, Tsutomu; Kamiyama, Tsuneo; Fukuchi, Yoshinosuke; Aoki, Takashi.

In: Infection and Immunity, Vol. 71, No. 3, 01.03.2003, p. 1234-1241.

Research output: Contribution to journalArticle

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, vol. 71, no. 3, pp. 1234-1241. https://doi.org/10.1128/IAI.71.3.1234-1241.2003
Miyahira, Yasushi ; Katae, Masaharu ; Takeda, Kazuyoshi ; Yagita, Hideo ; Okumura, Ko ; Kobayashi, Seiki ; Takeuchi, Tsutomu ; Kamiyama, Tsuneo ; Fukuchi, Yoshinosuke ; Aoki, Takashi. / Activation of natural killer T cells by α-galactosylceramide impairs DNA vaccine-induced protective immunity against Trypanosoma cruzi. In: Infection and Immunity. 2003 ; Vol. 71, No. 3. pp. 1234-1241.
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