| First Author | Van Der Sluijs KF | Year | 2005 |
| Journal | Immunology | Volume | 114 |
| Issue | 1 | Pages | 112-20 |
| PubMed ID | 15606801 | Mgi Jnum | J:94687 |
| Mgi Id | MGI:3513700 | Doi | 10.1111/j.1365-2567.2004.02000.x |
| Citation | Van Der Sluijs KF, et al. (2005) Enhanced viral clearance in interleukin-18 gene-deficient mice after pulmonary infection with influenza A virus. Immunology 114(1):112-20 |
| abstractText | Summary 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. |
