| RRC ID |
1490
|
| 著者 |
Abe T, Hemmi H, Miyamoto H, Moriishi K, Tamura S, Takaku H, Akira S, Matsuura Y.
|
| タイトル |
Involvement of the Toll-like receptor 9 signaling pathway in the induction of innate immunity by baculovirus.
|
| ジャーナル |
J Virol
|
| Abstract |
We have previously shown that mice inoculated intranasally with a wild-type baculovirus (Autographa californica nuclear polyhedrosis virus [AcNPV]) are protected from a lethal challenge by influenza virus. However, the precise mechanism of induction of this protective immune response by the AcNPV treatment remained unclear. Here we show that AcNPV activates immune cells via the Toll-like receptor 9 (TLR9)/MyD88-dependent signaling pathway. The production of inflammatory cytokines was severely reduced in peritoneal macrophages (PECs) and splenic CD11c(+) dendritic cells (DCs) derived from mice deficient in MyD88 or TLR9 after cultivation with AcNPV. In contrast, a significant amount of alpha interferon (IFN-alpha) was still detectable in the PECs and DCs of these mice after stimulation with AcNPV, suggesting that a TLR9/MyD88-independent signaling pathway might also participate in the production of IFN-alpha by AcNPV. Since previous work showed that TLR9 ligands include bacterial DNA and certain oligonucleotides containing unmethylated CpG dinucleotides, we also examined the effect of baculoviral DNA on the induction of innate immunity. Transfection of the murine macrophage cell line RAW264.7 with baculoviral DNA resulted in the production of the inflammatory cytokine, while the removal of envelope glycoproteins from viral particles, UV irradiation of the virus, and pretreatment with purified baculovirus envelope proteins or endosomal maturation inhibitors diminished the induction of the immune response by AcNPV. Together, these results indicate that the internalization of viral DNA via membrane fusion mediated by the viral envelope glycoprotein, as well as endosomal maturation, which releases the viral genome into TLR9-expressing cellular compartments, is necessary for the induction of the innate immune response by AcNPV.
|
| 巻・号 |
79(5)
|
| ページ |
2847-58
|
| 公開日 |
2005-3-1
|
| DOI |
10.1128/JVI.79.5.2847-2858.2005
|
| PII |
79/5/2847
|
| PMID |
15709004
|
| PMC |
PMC548444
|
| MeSH |
Adaptor Proteins, Signal Transducing
Animals
Antigens, Differentiation / genetics
Antigens, Differentiation / physiology
Base Sequence
Cell Line
Cytokines / biosynthesis
DNA, Viral / genetics
DNA-Binding Proteins / deficiency
DNA-Binding Proteins / genetics
DNA-Binding Proteins / physiology*
Dendritic Cells / immunology
Endocytosis
Humans
Immunity, Innate*
Inflammation Mediators / metabolism
Interferon-alpha / biosynthesis
Macrophage Activation
Macrophages, Peritoneal / immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Differentiation Factor 88
NF-kappa B / metabolism
Nucleopolyhedroviruses / genetics
Nucleopolyhedroviruses / immunology*
Phagocytosis
Receptors, Cell Surface / deficiency
Receptors, Cell Surface / genetics
Receptors, Cell Surface / physiology*
Receptors, Immunologic / deficiency
Receptors, Immunologic / genetics
Receptors, Immunologic / physiology
Signal Transduction
Toll-Like Receptor 9
Transfection
Viral Fusion Proteins / genetics
Viral Fusion Proteins / immunology
|
| IF |
4.501
|
| 引用数 |
169
|
|
WOS 分野
|
VIROLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
RAW 264(RCB0535) |
