Dendritic cells respond to influenza virus through TLR7- and PKR-independent pathways.
Natural interferon-producing cells (IPC) secrete type I IFN (IFN-alpha and -beta) in response to influenza virus. This process is independent of viral replication and is mediated by Toll-like receptor 7 (TLR7), which recognizes single-stranded RNA (ssRNA). DC also express TLR7 but its function in DC response to influenza virus is unknown. To address this, we compared the DC and IPC responses to influenza virus and ssRNA oligoribonucleotides (ORN) that activate TLR7. When stimulated by ORN in vitro and in vivo, DC matured and produced inflammatory cytokines but not IFN-alpha. DC did secrete IFN-alpha in response to influenza virus. However, this response was independent of TLR7 signaling and required viral replication but not dsRNA-activated protein kinase (PKR). We conclude that DC and IPC are hard-wired to secrete IFN-alpha via different pathways, reflecting their complementary but distinct roles in anti-viral immunity.
Barchet
Winfried
W
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Krug
Anne
A
Cella
Marina
M
Newby
Celeste
C
Fischer
Jens A A
JA
Dzionek
Andrzej
A
Pekosz
Andrew
A
Colonna
Marco
M
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D007113:Immunity, Innate; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D016898:Interferon-alpha / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000819:agonists / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D009843:Oligoribonucleotides / Q000235:genetics / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000819:agonists / Q000276:immunology*; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D051199:Toll-Like Receptor 7; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology; D014779:Virus Replication; D019892:eIF-2 Kinase / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D016207:Cytokines; C085820:INS1 protein, influenza virus; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D009843:Oligoribonucleotides; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D017361:Viral Nonstructural Proteins; D019892:eIF-2 Kinase