Activation of Vα14⁺Natural Killer T Cells by α-Galactosylceramide Results in Development of Th1 Response and Local Host Resistance in Mice Infected with<i>Cryptococcus neoformans</i>

• Kazuyoshi Kawakami

  <!--label omitted: 1-->The First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa,1 and

• Yuki Kinjo

  <!--label omitted: 1-->The First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa,1 and

• Satomi Yara

  <!--label omitted: 1-->The First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa,1 and

• Yoshinobu Koguchi

  <!--label omitted: 1-->The First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa,1 and

• Kaori Uezu

  <!--label omitted: 1-->The First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa,1 and

• Toshinori Nakayama

  <!--label omitted: 2-->CREST (Core Research for Evolutional Science and Technology) Project, Department of Molecular Immunology, Graduate School of Medicine, Chiba University, Chiba,2 Japan

• Masaru Taniguchi

  <!--label omitted: 2-->CREST (Core Research for Evolutional Science and Technology) Project, Department of Molecular Immunology, Graduate School of Medicine, Chiba University, Chiba,2 Japan

• Atsushi Saito

  <!--label omitted: 1-->The First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa,1 and

• S. H. E. Kaufmann

  editor

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-GM 1 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.

Journal

• Infection and Immunity

  Infection and Immunity 69 (1), 213-220, 2001-01

  American Society for Microbiology

Keywords

• Infectious Diseases
• Immunology
• Microbiology
• Parasitology

Details

• CRID: 1362262946131072512
• NII Article ID: 30020828858
• DOI: 10.1128/iai.69.1.213-220.2001
• ISSN: 10985522
• ISSN: 00199567
• ISSN: http://id.crossref.org/issn/00199567
• Web Site: https://journals.asm.org/doi/pdf/10.1128/IAI.69.1.213-220.2001
• Data Source:
  • Crossref
  • CiNii Articles