Activation of innate defense against a paramyxovirus is mediated by RIG-I and TLR7 and TLR8 in a cell-type-specific manner.
Recognition of pathogens by the innate immune system is mediated by pattern recognition receptors (PRRs), which recognize specific molecular structures of the infectious agents and subsequently trigger expression of genes involved in host defense. Toll-like receptors (TLRs) represent a well-characterized class of membrane-bound PRRs, and the RNA helicase retinoic acid inducible gene I (RIG-I) has recently been described as a novel cytoplasmic PRR recognizing double-stranded RNA (dsRNA). Here we show that activation of signal transduction and induction of cytokine expression by the paramyxovirus Sendai virus is dependent on virus replication and involves PRRs in a cell-type-dependent manner. While nonimmune cells relied entirely on recognition of dsRNA through RIG-I for activation of an antiviral response, myeloid cells utilized both the single-stranded RNA sensing TLR7 and TLR8 and dsRNA-dependent mechanisms independent of RIG-I, TLR3, and dsRNA-activated protein kinase R to trigger this response. Therefore, there appears to be a large degree of cell-type specificity in the mechanisms used by the host to recognize infecting viruses.
Melchjorsen
Jesper
J
Department of Medical Microbiology and Immunology, University of Aarhus, Denmark.
Jensen
Søren B
SB
Malmgaard
Lene
L
Rasmussen
Simon B
SB
Weber
Friedemann
F
Bowie
Andrew G
AG
Matikainen
Sampsa
S
Paludan
Søren R
SR
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D006801:Humans; D007113:Immunity, Innate; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology*; D051379:Mice; D020365:RNA Helicases / Q000378:metabolism / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D010253:Respirovirus Infections / Q000276:immunology*; D029082:Sendai virus / Q000276:immunology* / Q000502:physiology; D015398:Signal Transduction; D013045:Species Specificity; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051193:Toll-Like Receptors; D014779:Virus Replication
D016207:Cytokines; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495344:TLR3 protein, human; C495348:TLR7 protein, human; C495349:TLR8 protein, human; C477038:Tlr7 protein, mouse; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051193:Toll-Like Receptors; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases