Involvement of endogenously synthesized interleukin (IL)-18 in the protective effects of IL-12 against pulmonary infection with Cryptococcus neoformans in mice

Kazuyoshi Kawakami, Mahboob Hossain Qureshi, Tiantuo Zhang, Yoshinobu Koguchi, Satomi Yara, Kiyoshi Takeda, Shizuo Akira, Masashi Kurimoto, Atsushi Saito

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16 Citations (Scopus)

Abstract

We previously demonstrated that interleukin (IL)-12 protected mice against fatal pulmonary infection with a highly virulent strain of Cryptococcus neoformans, which correlated well with the production of interferon (IFN)-γ as well as IL-18 in the primary infected site. In the present study, we examined the role of endogenously synthesized IL-18 in IL-12-induced host resistance to this pathogen. There was little or no production of IFN-γ and IL-18 both at mRNA and protein levels in lungs of mice infected with C. neoformans, while treatment with IL-12 induced a marked production of these cytokines. Caspase-1 mRNA was expressed in infected mice even without IL-12 treatment. Administration of neutralizing anti-IFN-γ monoclonal antibody (mAb) clearly inhibited production of IFN-γ and IL-18 induced by IL-12, while control IgG did not show such an effect. However, administration of IFN-γ did not induce the production of both cytokines in infected mice, although tumor necrosis factor (TNF)-α and IFN-γ-inducible protein (IP)-10 were synthesized by the same treatment. Finally, neutralizing anti-IL-18 antibody (Ab) significantly interfered with the production of IFN-γ and elimination of the microorganism from the lung induced by IL-12 treatment. Furthermore, both IFN-γ synthesis and host protection caused by IL-12 were profoundly diminished in IL-18 gene-disrupted mice. Considered collectively, our results indicated that host protection against C. neoformans induced by IL-12 involved endogenously synthesized IL-18 and that the production of IL-18 was mediated at least in part by endogenous IFN-γ. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)191-200
Number of pages10
JournalFEMS Immunology and Medical Microbiology
Volume27
Issue number3
DOIs
Publication statusPublished - 2000 Mar

Keywords

  • Cryptococcus neoformans
  • Host defense
  • Interferon-γ
  • Interleukin-12
  • Interleukin-18
  • Lung

ASJC Scopus subject areas

  • Immunology and Allergy
  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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