Toll-like receptor-mediated activation of neutrophils by influenza A virus
Department of Medicine, Division of Infectious Diseases and Immunology; Department of Pediatrics
Animals; Cell Line; Cytokines; Granulocyte Macrophage Colony-Stimulating Factors,; Recombinant; Humans; Immunity, Innate; Influenza A Virus, H3N2 Subtype; Ligands; Macrolides; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophil Activation; Neutrophils; RNA, Viral; Toll-Like Receptor 7; Toll-Like Receptor 8; Toll-Like Receptors; Virus Internalization; Virus Replication
Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
Blood. 2008 Sep 1;112(5):2028-34. Epub 2008 Jun 10. Link to article on publisher's site
Wang JP, Bowen GN, Padden C, Cerny AM, Finberg RW, Newburger PE, Kurt-Jones EA. (2008). Toll-like receptor-mediated activation of neutrophils by influenza A virus. Open Access Publications by UMMS Authors. https://doi.org/10.1182/blood-2008-01-132860. Retrieved from https://escholarship.umassmed.edu/oapubs/2055