TY - JOUR
T1 - Activation of natural killer T cells by α-galactosylceramide impairs DNA vaccine-induced protective immunity against Trypanosoma cruzi
AU - Miyahira, Yasushi
AU - Katae, Masaharu
AU - Takeda, Kazuyoshi
AU - Yagita, Hideo
AU - Okumura, Ko
AU - Kobayashi, Seiki
AU - Takeuchi, Tsutomu
AU - Kamiyama, Tsuneo
AU - Fukuchi, Yoshinosuke
AU - Aoki, Takashi
PY - 2003/3/1
Y1 - 2003/3/1
N2 - 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.
AB - 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.
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U2 - 10.1128/IAI.71.3.1234-1241.2003
DO - 10.1128/IAI.71.3.1234-1241.2003
M3 - Article
C2 - 12595437
AN - SCOPUS:0037371320
SN - 0019-9567
VL - 71
SP - 1234
EP - 1241
JO - Infection and Immunity
JF - Infection and Immunity
IS - 3
ER -
