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Publication : Toll-like receptor-mediated activation of neutrophils by influenza A virus.

First Author  Wang JP Year  2008
Journal  Blood Volume  112
Issue  5 Pages  2028-34
PubMed ID  18544685 Mgi Jnum  J:138732
Mgi Id  MGI:3806208 Doi  10.1182/blood-2008-01-132860
Citation  Wang JP, et al. (2008) Toll-like receptor-mediated activation of neutrophils by influenza A virus. Blood 112(5):2028-34
abstractText  Influenza virus infection of the respiratory tract is characterized by a neutrophil infiltrate accompanied by inflammatory cytokine and chemokine production. We and others have reported that Toll-like receptor (TLR) proteins are present on human neutrophils and that granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment enhances IL-8 (CXCL8) secretion in response to stimulation with TLR ligands. We demonstrate that influenza virus can induce IL-8 and other inflammatory cytokines from GM-CSF-primed human neutrophils. Using heat inactivation of influenza virus, we show that viral entry but not replication is required for cytokine induction. Furthermore, endosomal acidification and viral uncoating are necessary. Finally, using single-cell analysis of intracellular cytokine accumulation in neutrophils from knockout mice, we prove that TLR7 is essential for influenza viral recognition and inflammatory cytokine production by murine neutrophils. These studies demonstrate neutrophil activation by influenza virus and highlight the importance of TLR7 and TLR8 in that response.
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