title: Activation of natural killer T cells by alpha-galactosylceramide impairs DNA vaccine-induced protective immunity against Trypanosoma cruzi.
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.
authors.affiliation: Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan. miyahira@med.juntendo.ac.jp
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miyahira
authors.forename: Masaharu
authors.initials: M
authors.lastname: Katae
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Seiki
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Kamiyama
authors.forename: Yoshinosuke
authors.initials: Y
authors.lastname: Fukuchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Aoki
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000502:physiology; D055610:Antigens, CD1d; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D014355:Chagas Disease / Q000276:immunology / Q000401:mortality; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016052:Protozoan Vaccines / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; D005699:Galactosylceramides; D016052:Protozoan Vaccines; D019444:Vaccines, DNA