IL-18 Protects Mice Against Pulmonary and Disseminated Infection with Cryptococcus neoformans by Inducing IFN-γ Production

Kazuyoshi Kawakami, Mahboob Hossain Qureshi, Tiantuo Zhang, Haruki Okamura, Masashi Kurimoto, Atsushi Saito

Research output: Contribution to journalArticle

166 Citations (Scopus)

Abstract

We examined the effects of a newly identified cytokine, IL-18, originally designated as IFN-γ-inducing factor, in a mouse model of pulmonary and disseminated infection with a highly virulent strain of Cryptococcus neoformans. Administration of murine rIL-18 enhanced elimination of live micro-organisms from the lungs, prevented fungal dissemination to the brain, reduced the level of serum cryptococcal capsular polysaccharide Ags, and increased the survival rate of infected mice. Histologic examination of lung sections of infected and PBS-treated mice showed a poor cellular inflammatory reaction and a large number of multiplying C. neoformans yeast cells in alveolar spaces. In contrast, massive infiltration of inflammatory cells, consisting mainly of mononuclear cells, characterized sections of lungs of infected animals treated with IL-18. Treatment with IL-18 also increased the level of serum IFN-γ. In addition, the protective effect of IL-18 on cryptococcal infection was abrogated by administration of neutralizing anti-IFN-γ mAb. Finally, we examined the effect of neutralizing anti-IL-18 Ab on cryptococcal infection to define the physiologic role of this cytokine in host defense using another weakly virulent strain of C. neoformans, which induced the expression of IL-18 mRNA in the infected lungs. Administration of this Ab exacerbated the infection, as shown by the increased lung burden. Our results indicate that IL-18 plays an important role in host defense against infection with C. neoformans.

Original languageEnglish
Pages (from-to)5528-5534
Number of pages7
JournalJournal of Immunology
Volume159
Issue number11
Publication statusPublished - 1997 Dec 1
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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