Flavivirus activation of plasmacytoid dendritic cells delineates key elements of TLR7 signaling beyond endosomal recognition
Authors
Wang, Jennifer P.Liu, Ping
Latz, Eicke
Golenbock, Douglas T.
Finberg, Robert W.
Libraty, Daniel H.
UMass Chan Affiliations
Center for Infectious Disease and Vaccine ResearchDepartment of Medicine, Division of Infectious Diseases and Immunology
Document Type
Journal ArticlePublication Date
2006-11-04Keywords
AdultAnimals
Cell Line
Dendritic Cells
Dengue Virus
Dogs
Endosomes
Humans
Hydrogen-Ion Concentration
Influenza A virus
Interferon-alpha
Interleukin-8
Mice
Mice, Inbred C57BL
Mice, Knockout
NF-kappa B
RNA, Viral
*Signal Transduction
Toll-Like Receptor 7
Viral Fusion Proteins
Virus Activation
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
TLR7 senses RNA in endosomal compartments. TLR7 expression and signaling have been demonstrated in plasmacytoid and myeloid dendritic cells, B cells, and T cells. The regulation of TLR7 signaling can play a crucial role in shaping the immune response to RNA viruses with different cellular tropisms, and in developing adjuvants capable of promoting balanced humoral and cell-mediated immunity. We used unique characteristics of two ssRNA viruses, dengue virus and influenza virus, to delineate factors that regulate viral RNA-human TLR7 signaling beyond recognition in endosomal compartments. Our data show that TLR7 recognition of enveloped RNA virus genomes is linked to virus fusion or uncoating from the endosome. The signaling threshold required to activate TLR7-type I IFN production is greater than that required to activate TLR7-NF-kappaB-IL-8 production. The higher order structure of viral RNA appears to be an important determinant of TLR7-signaling potency. A greater understanding of viral RNA-TLR7 activity relationships will promote rational approaches to interventional and vaccine strategies for important human viral pathogens.Source
J Immunol. 2006 Nov 15;177(10):7114-21.
DOI
10.4049/jimmunol.177.10.7114Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38202PubMed ID
17082628Related Resources
ae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.177.10.7114