Original Literature | Model OverView |
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Publication
Title
Viral immunity: cross-priming with the help of TLR3.
Affiliation
Tumour Immunology Unit, Cancer Research UK, Weatherall Institute of MolecularMedicine, John Radcliffe Hospital, Oxford OX3 9DS, UK.mariolina.salio@molecular-medicine.oxford.ac.uk
Abstract
Cross-presentation is important for regulating T-cell responses to exogenousantigens and can maintain tolerance (cross-tolerance) or induce immune responses(cross-priming). Recent exciting results on the role of the Toll-like receptorTLR3 in promoting cross-priming of viral antigens provide new insights into themechanisms that allow Toll-like receptor signaling to bridge innate and adaptiveimmune responses.
PMID
15886091
|
Entity
cytokines
--
MO000019387
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csml-variable:Double
m3957
10
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TRANSPATH | MO000019387 |
--
dsRNA:TLR3
--
MO000041446
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m19314
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TRANSPATH | MO000041446 |
--
--
e1
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane
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--
--
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m1
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e10
cso30:c:EntityBiologicalCompartment
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genes of co-stimulatory molecules
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e11
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NF-kappaB {activated}
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TRANSPATH | MO000000058 |
--
IFN Type I
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TLR ligand: TLR
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e5
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e54
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m54
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e55
cso30:c:EntityBiologicalCompartment
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m55
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e56
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Nucleoplasm
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--
--
csml-variable:Double
m56
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cytokine
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e62
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m62
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e7
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csml-variable:Double
m7
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p1
p1
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--
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stoichiometry:c13 : 1
m3957*m93228*m11*0.1
nodelay
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0
PMID: 15886091 TLR signaling induces a significant change in the phenotype of DCs, referred to as DC maturation. PMID: 15886091 This process is characterized by enhanced expression of co-stimulatory molecules and major histocompatibility complex (MHC)?peptide complexes, and increased secretion of cytokines necessary for activation and polarization of naive T cells (i.e. T cells that have never responded to antigen).
p10
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--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c24 : 1
stoichiometry:c25 : 1
stoichiometry:c26 : 1
m119368*m36179*0.1
nodelay
--
0
PMID: 15886091 In the case of viruses capable of infecting DCs, a TLR-independent recognition of dsRNA occurs. It has been shown that PKR and RNAseL are involved in this alternative pathway, which may synergize with TLR3 signaling.
p11
p11
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cso30:i:CC_Cytosol
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--
and
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stoichiometry:c27 : 1
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m6*m19314*0.1
nodelay
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PMID: 15886091, 15711573 As TLR3 is predominantly expressed in CD8¦Á+ DCs in mice, Reis e Sousa and colleagues [10] set out to investigate whether recognition of dsRNA in apoptotic bodies from virus-infected cells allows CD8¦Á+ DCs to prime an immune response to viruses that are unable to infect DCs directly. CD8alpha+ DCs underwent phenotypic maturation and secreted inflammatory cytokines when exposed to apoptotic cells loaded with dsRNA but not to unloaded controls.
p2
p2
cso30:i:ME_Binding
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--
--
and
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m3965*m119368*0.1
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PMID: 15886091, 11607032 TLR3 is an endosomal Toll-like receptor that recognizes double-stranded (ds) RNA [11], a by-product of most viral infections.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c6 : 1
stoichiometry:c7 : 1
stoichiometry:c5 : 1
m6*m5*0.1
nodelay
--
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PMID: 15886091 This process is characterized by enhanced expression of co-stimulatory molecules and major histocompatibility complex (MHC)?peptide complexes, and increased secretion of cytokines necessary for activation and polarization of naive T cells (i.e. T cells that have never responded to antigen).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c8 : 1
m5*0.1
nodelay
--
0
PMID: 15886091 This process is characterized by enhanced expression of co-stimulatory molecules and major histocompatibility complex (MHC)?peptide complexes, and increased secretion of cytokines necessary for activation and polarization of naive T cells (i.e. T cells that have never responded to antigen).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c11 : 1
stoichiometry:c9 : 1
m5*0.1
nodelay
--
0
PMID: 15886091 This process is characterized by enhanced expression of co-stimulatory molecules and major histocompatibility complex (MHC)?peptide complexes, and increased secretion of cytokines necessary for activation and polarization of naive T cells (i.e. T cells that have never responded to antigen).
p6
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m12*m19314*0.1
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--
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PMID: 15886091 The viral dsRNA contained within the apoptotic bodies is recognized by endosomal TLR3, inducing NFkappaB activation and DC maturation.
p7
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--
--
and
mass
coefficient1:0.1
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stoichiometry:c20 : 1
m19314*m1634*0.1
nodelay
--
0
PMID: 15886091 The viral dsRNA contained within the apoptotic bodies is recognized by endosomal TLR3, inducing NFkappaB activation and DC maturation PMID: 15886091 DC maturation and cross-priming can be enhanced by type I IFN released by infected cells. PMID: 15886091, 15711573 In a recent paper published in Nature [10], the group of Reis e Sousa has shed some light on this issue and elegantly demonstrated that signaling via TLR3 promotes cross-priming of virus-specific T-cell responses by ensuring the maturation of immature CD8alpha+ DCs that have taken up apoptotic bodies from virus-infected cells.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c18 : 1
stoichiometry:c19 : 1
m14*0.1
nodelay
--
0
PMID: 15886091 DC maturation and cross-priming can be enhanced by type I IFN released by infected cells.
p9
p9
cso30:i:ME_Binding
cso30:i:CC_Extracellular
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--
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mass
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stoichiometry:c21 : 1
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stoichiometry:c23 : 1
m119368*m1055*0.1
nodelay
--
0
PMID: 15886091 In the case of viruses capable of infecting DCs, a TLR-independent recognition of dsRNA occurs. It has been shown that PKR and RNAseL are involved in this alternative pathway, which may synergize with TLR3 signaling.
cso30:c:InputAssociation
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