Toll-like receptor–mediated activation of neutrophils by influenza A virus
Open Access
- 1 September 2008
- journal article
- Published by American Society of Hematology in Blood
- Vol. 112 (5), 2028-2034
- https://doi.org/10.1182/blood-2008-01-132860
Abstract
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.Keywords
This publication has 39 references indexed in Scilit:
- Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virusNature, 2007
- Dendritic cells respond to influenza virus through TLR7‐ and PKR‐independent pathwaysEuropean Journal of Immunology, 2004
- Use of murine embryonic fibroblasts to define Toll-like receptor activation and specificityInnate Immunity, 2004
- Use of murine embryonic fibroblasts to define Toll-like receptor activation and specificityInnate Immunity, 2004
- Intact Gram-NegativeHelicobacter pylori,Helicobacter felis, andHelicobacter hepaticusBacteria Activate Innate Immunity via Toll-Like Receptor 2 but Not Toll-Like Receptor 4Infection and Immunity, 2004
- Innate Antiviral Responses by Means of TLR7-Mediated Recognition of Single-Stranded RNAScience, 2004
- Toll-like receptors stimulate human neutrophil functionBlood, 2003
- The Toll‐like receptor 7 (TLR7)‐specific stimulus loxoribine uncovers a strong relationship within the TLR7, 8 and 9 subfamilyEuropean Journal of Immunology, 2003
- Global Impact of Influenza Virus on Cellular Pathways Is Mediated by both Replication-Dependent and -Independent EventsJournal of Virology, 2001
- Inhibitory effect of bafilomycin A1, a specific inhibitor of vacuolar-type proton pump, on the growth of influenza A and B viruses in MDCK cellsAntiviral Research, 1995