Abstract
Viral infection of mammalian host results in the activation of innate immune responses. Toll-like receptors (TLRs) have been shown to mediate the recognition of many types of pathogens, including viruses. The genomes of viruses possess unique characteristics that are not found in mammalian genomes, such as high CpG content and double-stranded RNA. These genomic nucleic acids serve as molecular signatures associated with viral infections. Here we show that TLR7 recognizes the single-stranded RNA viruses, vesicular stomatitis virus and influenza virus. The recognition of these viruses by plasmacytoid dendritic cells and B cells through TLR7 results in their activation of costimulatory molecules and production of cytokines. Moreover, this recognition required intact endocytic pathways. Mice deficient in either the TLR7 or the TLR adaptor protein MyD88 demonstrated reduced responses to in vivo infection with vesicular stomatitis virus. These results demonstrate microbial ligand recognition by TLR7 and provide insights into the pathways used by the innate immune cells in the recognition of viral pathogens.
Publication types
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, P.H.S.
MeSH terms
- Adaptor Proteins, Signal Transducing
- Animals
- Antigens, Differentiation / metabolism
- Bone Marrow Cells / immunology
- Chick Embryo
- Chloroquine / pharmacology
- Cytokines / biosynthesis
- Dendritic Cells / immunology
- Endosomes / immunology
- Endosomes / virology
- Interferon-alpha / metabolism
- Macrophages / immunology
- Membrane Glycoproteins / deficiency
- Membrane Glycoproteins / genetics
- Membrane Glycoproteins / immunology*
- Mice
- Mice, Knockout
- Myeloid Differentiation Factor 88
- Orthomyxoviridae / genetics
- Orthomyxoviridae / immunology*
- Peritoneum / cytology
- RNA, Viral / genetics
- RNA, Viral / immunology*
- Receptors, Cell Surface / deficiency
- Receptors, Cell Surface / genetics
- Receptors, Cell Surface / immunology*
- Receptors, Immunologic / metabolism
- Rhabdoviridae Infections / immunology
- Spleen / cytology
- Toll-Like Receptor 7
- Vesicular stomatitis Indiana virus / genetics
- Vesicular stomatitis Indiana virus / immunology*
Substances
- Adaptor Proteins, Signal Transducing
- Antigens, Differentiation
- Cytokines
- Interferon-alpha
- Membrane Glycoproteins
- Myd88 protein, mouse
- Myeloid Differentiation Factor 88
- RNA, Viral
- Receptors, Cell Surface
- Receptors, Immunologic
- Tlr7 protein, mouse
- Toll-Like Receptor 7
- Chloroquine