CovidV1, Main, Exploration, bibRecord, 001002

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

Identifieur interne : 001002 ( Main/Exploration ); précédent : 001001; suivant : 001003

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

Auteurs : Koenraad F. Van Der Sluijs [Pays-Bas] ; Leontine J R. Van Elden [Pays-Bas] ; Ramon Arens [Pays-Bas] ; Monique Nijhuis [Pays-Bas] ; Rob Schuurman [Pays-Bas] ; Sandrine Florquin [Pays-Bas] ; Joan Kwakkel [Pays-Bas] ; Shizuo Akira [Japon] ; Henk M. Jansen [Pays-Bas] ; René Lutter [Pays-Bas] ; Tom Van Der Polls [Pays-Bas]

Source :

Immunology [ 0019-2805 ] ; 2005.

RBID : PMC:1782065

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-γ (IFN-γ) levels were similar in the lungs of IL-18^–/– mice and wildtype mice. Intracellular IFN-γ staining revealed similar expression levels in lung-derived natural killer cells, CD4⁺ and CD8⁺ T cells, indicating that IFN-γ production is IL-18-independent during influenza virus infection. Tumour necrosis factor-α 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.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1782065

DOI: 10.1111/j.1365-2567.2004.02000.x
PubMed: 15606801
PubMed Central: 1782065

Affiliations:

Japon, Pays-Bas

Le document en format XML

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<front><div type="abstract" xml:lang="en"><p>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 <italic>in vitro</italic>
, 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<sup>–/–</sup>
) 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<sup>–/–</sup>
 mice. This enhanced viral clearance correlated with increased CD4<sup>+</sup>
 T-cell activation in the lungs as reflected by CD69 expression on the cell surface. Surprisingly, interferon-γ (IFN-γ) levels were similar in the lungs of IL-18<sup>–/–</sup>
 mice and wildtype mice. Intracellular IFN-γ staining revealed similar expression levels in lung-derived natural killer cells, CD4<sup>+</sup>
 and CD8<sup>+</sup>
 T cells, indicating that IFN-γ production is IL-18-independent during influenza virus infection. Tumour necrosis factor-α production by CD4<sup>+</sup>
 T cells was significantly lower in IL-18<sup>–/–</sup>
 mice than in wildtype mice. Our data indicate that endogenous IL-18 impairs viral clearance during influenza A infection.</p>
</div>
</front>
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<name sortKey="Van Der Sluijs, Koenraad F" sort="Van Der Sluijs, Koenraad F" uniqKey="Van Der Sluijs K" first="Koenraad F" last="Van Der Sluijs">Koenraad F. Van Der Sluijs</name>
<name sortKey="Van Elden, Leontine J R" sort="Van Elden, Leontine J R" uniqKey="Van Elden L" first="Leontine J R" last="Van Elden">Leontine J R. Van Elden</name>
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<country name="Japon"><noRegion><name sortKey="Akira, Shizuo" sort="Akira, Shizuo" uniqKey="Akira S" first="Shizuo" last="Akira">Shizuo Akira</name>
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Enhanced viral clearance in interleukin-18 gene-deficient mice after pulmonary infection with influenza A virus

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

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