Toll-like receptor 3 is induced by and mediates antiviral activity against rhinovirus infection of human bronchial epithelial cells.
Rhinoviruses (RV) are the major cause of the common cold and acute exacerbations of asthma and chronic obstructive pulmonary disease. Toll-like receptors (TLRs) are a conserved family of receptors that recognize and respond to a variety of pathogen-associated molecular patterns. TLR3 recognizes double-stranded RNA, an important intermediate of many viral life cycles (including RV). The importance of TLR3 in host responses to virus infection is not known. Using BEAS-2B (a human bronchial epithelial cell-line), we demonstrated that RV replication increased the expression of TLR3 mRNA and TLR3 protein on the cell surface. We observed that blocking TLR3 led to a decrease in interleukin-6, CXCL8, and CCL5 in response to poly(IC) but an increase following RV infection. Finally, we demonstrated that TLR3 mediated the antiviral response. This study demonstrates an important functional requirement for TLR3 in the host response against live virus infection and indicates that poly(IC) is not always a good model for studying the biology of live virus infection.
Hewson
Christopher A
CA
Department of Respiratory Medicine, National Heart and Lung Institute and Wright Fleming Institute of Infection and Immunity, Imperial College London, Norfolk Place, London W2 1PG, United Kingdom.
Jardine
Alice
A
Edwards
Michael R
MR
Laza-Stanca
Vasile
V
Johnston
Sebastian L
SL
D001980:Bronchi / Q000166:cytology / Q000276:immunology / Q000821:virology; D002460:Cell Line; D018946:Chemokine CCL5; D019742:Chemokines, CC / Q000032:analysis; D019743:Chemokines, CXC / Q000032:analysis; D005434:Flow Cytometry; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012229:Rhinovirus / Q000276:immunology*; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors
C483024:CCL5 protein, human; D018946:Chemokine CCL5; D019742:Chemokines, CC; D019743:Chemokines, CXC; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors