Activation of Vα14+ natural killer T cells by α-galactosylceramide results in development of Th1 response and local host resistance in mice infected with Cryptococcus neoformans

K. Kawakami, Y. Kinjo, S. Yara, Y. Koguchi, K. Uezu, T. Nakayama, M. Taniguchi, A. Saito

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130 Citations (Scopus)

Abstract

We examined the effect of α-galactosylceramide (α- GalCer) on the synthesis of gamma interferon (IFN-γ) and local resistance in mice infected intravenously with Cryptococcus neoformans. The level of IFN-γ in serum increased on day 3, reached a peak level on day 7, and decreased to the basal level on day 14 postinfection in mice treated with α-GalCer, while in vehicle-treated mice, no increase was detected at any time points except for a small increase on day 7. Such effects were not observed in NKT-KO mice. In CD4KO mice, minor synthesis of IFN-γ was detected on day 3 in sera but was completely abolished by day 7. The α-GalCer-induced IFN-γ production on day 3 was partially reduced in mice depleted of NK cells by treatment with anti-asialo-GM1 antibody (Ab). Spleen cells obtained from infected and α- GalCer-treated mice on day 7 produced a large amount of IFN-γ upon restimulation with live organisms, while only a marginal level of production was detected in splenocytes from infected and vehicle-treated mice. Such effects were abolished in CD4KO and NKT-KO mice. Finally, the fungal loads in the lungs and spleen on days 7 and 14 were significantly reduced in α. GalCer-treated mice compared to those in control mice. In NKT. KO mice, local resistance elicited by α-GalCer was completely abolished, although no obvious exacerbation of infection was detected. Furthermore, treatment with anti-IFN-γ monoclonal Ab mostly abrogated the protective effect of this agent. Thus, our results indicated that activation of Vα14+ NKT cells resulted in an increased Th1 response and local resistance to C. neoformans through production of IFN-γ.

Original languageEnglish
Pages (from-to)213-220
Number of pages8
JournalInfection and immunity
Volume69
Issue number1
DOIs
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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