Influenza a viruses upregulate neutrophil toll-like receptor 2 expression and function.
Neutrophils are involved in the initial host response to influenza A virus (IAV) infection and exhibit both activation and depressed function after exposure to the virus. We demonstrate that IAV causes rapid upregulation of Toll-like receptor 2 (TLR2) expression on neutrophils. The neutrophil agonists, formyl-methylpleucyl-alanine (fMLP), C5a and lipopolysaccharide did not alter neutrophil TLR2 expression, whereas PMA and the microbial TLR2 ligands, peptidoglycan (PGN) and zymosan, reduced it. To determine the functional significance of IAV-induced increase in TLR2 expression, IAV-treated neutrophils were exposed to PGN, Staphylococcus aureus (S. aureus) and zymosan. Pretreatment with IAV resulted in significantly increased uptake of S. aureus and zymosan and accelerated neutrophil apoptosis when combined with S. aureus. IAV-treated cells generated significantly more H(2)O(2) in response to PGN. These results indicate that IAV increases neutrophil surface expression of TLR2 and modulates functional responses to ligands that bind TLR2. These findings may clarify IAV-induced perturbation of neutrophil functions in vivo.
Department of Medicine, Section of Hematology/Oncology, Boston University School of Medicine, Boston, MA 02118, USA.
R M
RM
Lee
M R
MR
White
K L
KL
Hartshorn
D015936:Complement C5a / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D010457:Peptidoglycan / Q000494:pharmacology; D037662:Pulmonary Surfactant-Associated Protein A / Q000494:pharmacology; D044087:Receptor, Anaphylatoxin C5a / Q000276:immunology; D011951:Receptors, Complement / Q000096:biosynthesis / Q000276:immunology; D016897:Respiratory Burst / Q000187:drug effects / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000276:immunology*; D015854:Up-Regulation; D015054:Zymosan / Q000494:pharmacology
C488033:C5AR1 protein, human; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D010457:Peptidoglycan; D037662:Pulmonary Surfactant-Associated Protein A; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D051195:Toll-Like Receptor 2; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D015054:Zymosan