Enhanced viral clearance in interleukin-18 gene-deficient mice after pulmonary infection with influenza A virus

KF Van der Sluijs*, LJR Van Elden, R Arens, M Nijhuis, R Schuurman, S Florquin, S Akira, HM Jansen, R Lutter, T Van Der Polls

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

38 Citations (Scopus)

Abstract

T helper 1 driven immune responses facilitate host defence during viral infections. Because interleukin-18 (IL-18) mediates T helper 1 driven immune responses, and since mature IL-18 is up-regulated in human macrophages after influenza virus infection in vitro, it has been suggested that IL-18 plays an important role in the immune response to influenza. To determine the role of IL-18 in respiratory tract infection with influenza, IL-18 gene-deficient (IL-18(-/-)) and normal wildtype mice were intranasally inoculated with influenza A virus. Influenza resulted in an increase in constitutively expressed IL-18 in the lungs of wildtype mice. The clearance of influenza A was inhibited by IL-18, as indicated by reduced viral loads on day 8 and day 12 after infection in IL-18(-/-) mice. This enhanced viral clearance correlated with increased CD4(+) T-cell activation in the lungs as reflected by CD69 expression on the cell surface. Surprisingly, interferon-gamma (IFN-gamma) levels were similar in the lungs of IL-18(-/-) mice and wildtype mice. Intracellular IFN-gamma staining revealed similar expression levels in lung-derived natural killer cells, CD4(+) and CD8(+) T cells, indicating that IFN-gamma production is IL-18-independent during influenza virus infection. Tumour necrosis factor-alpha production by CD4(+) T cells was significantly lower in IL-18(-/-) mice than in wildtype mice. Our data indicate that endogenous IL-18 impairs viral clearance during influenza A infection.

Original languageEnglish
Pages (from-to)112-120
Number of pages9
JournalImmunology
Volume114
Issue number1
DOIs
Publication statusPublished - Jan-2005

Keywords

  • influenza
  • lung
  • cytokine
  • inflammation
  • GAMMA-INDUCING FACTOR
  • HUMAN T-CELLS
  • MEDIATED CYTOTOXICITY
  • CYTOKINE PRODUCTION
  • HUMAN MACROPHAGES
  • HOST-DEFENSE
  • IL-18
  • EXPRESSION
  • ACTIVATION
  • TH1

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