1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/15886091.csml convertedTime:2009.07.01.10:51

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Viral immunity: cross-priming with the help of TLR3.
Authors Salio M, Cerundolo V.
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
Model Abstract

Entity

G010240:MHC MO000000058:NF-kappaB MO000008179:PKR MO000016658:IFN Type I MO000019387:cytokines MO000019398:TLR3 MO000022224:dsRNA MO000022225:dsRNA:PKR MO000041446:dsRNA:TLR3 MO000061281:RNASEL e1: e10: e11:genes of co-stimulatory molecules e12:NF-kappaB {activated} e13:IFN Type I e14:dsRNA: RNASEL e2: e3: e4: e5:TLR ligand: TLR e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:cytokine e60: e61: e62: e7: e8: e9:

Process

p1 p10 p11 p2 p3 p4 p5 p6 p7 p8 p9
Model Detail
453.0, 785.0
30.0, 30.0

MHC

--

G010240

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p4

p1

true true true true

csml-variable:Double

m93228

10

false

infinite

0

unit false false false
TRANSFACG010240

--

Go back
500.0, 220.0
28.0, 28.0

NF-kappaB

--

MO000000058

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p6

true true true true

csml-variable:Double

m12

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
325.0, 167.0
29.0, 29.0

PKR

--

MO000008179

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p9

true true true true

csml-variable:Double

m1055

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000008179

--

Go back
149.0, 501.0
30.0, 30.0

IFN Type I

--

MO000016658

cso30:c:Protein

cso30:i:CC_CellComponent

--

p8

p7

true true true true

csml-variable:Double

m1634

10

false

infinite

0

unit false false false
TRANSPATHMO000016658

--

Go back
130.0, 702.0
28.0, 28.0

cytokines

--

MO000019387

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m3957

10

false

infinite

0

unit false false false
TRANSPATHMO000019387

--

Go back
381.0, 113.0
30.0, 30.0

TLR3

--

MO000019398

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p2

true true true true

csml-variable:Double

m3965

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019398

--

Go back
446.0, 6.0
28.0, 28.0

dsRNA

--

MO000022224

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p2 p9 p10

true true true true

csml-variable:Double

m119368

10

false

infinite

0

unit false false false
TRANSPATHMO000022224

--

Go back
260.0, 166.0
32.0, 32.0

dsRNA:PKR

--

MO000022225

cso30:c:Protein

cso30:i:CC_CellComponent

--

p9

--

true true true true

csml-variable:Double

m6524

10

false

infinite

0

unit false false false
TRANSPATHMO000022225

--

Go back
444.0, 100.0
32.0, 32.0

dsRNA:TLR3

--

MO000041446

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m19314

10

false

infinite

0

unit false false false
TRANSPATHMO000041446

--

Go back
545.0, 171.0
30.0, 30.0

RNASEL

--

MO000061281

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p10

true true true true

csml-variable:Double

m36179

10

false

infinite

0

unit false false false
TRANSPATHMO000061281

--

Go back
203.75272069268271, 99.11747036707945
598.1684562202878, 868.5405984318578

--

e1

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane

--

--

--

true true true true

csml-variable:Double

m1

0

false

infinite

0

unit false true false

--

Go back
209.51603211926417, 112.39271124119229
579.8084090987795, 815.6273984238221

--

e10

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytosol

--

--

--

true true true true

csml-variable:Double

m10

0

false

infinite

0

unit false true false

--

Go back
501.5, 748.0
45.0, 24.0

genes of co-stimulatory molecules

--

e11

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p5

p1

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
500.0, 272.0
28.0, 28.0

NF-kappaB {activated}

--

e12

cso30:c:Protein

cso30:i:CC_CellComponent

--

p6

--

true true true true

csml-variable:Double

m13

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
503.5, 633.0
40.95155709342561, 21.84083044982699

IFN Type I

--

e13

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p8

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
603.625, 149.5
40.44888351941343, 49.52924512581235

dsRNA: RNASEL

--

e14

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p10

--

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
203.75272069268271, 99.11747036707945
598.1684562202878, 868.5405984318578

--

e2

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m2

0

false

infinite

0

unit false true false

--

Go back
215.71608981708843, 111.08083949148524
574.2417179714762, 844.6138601830468

--

e3

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m3

0

false

infinite

0

unit false true false

--

Go back
237.84832269723918, 132.01673545919522
529.977252211175, 802.7420682476261

--

e4

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m4

0

false

infinite

0

unit false true false

--

Go back
760.5, 588.0
39.66705549075154, 48.57190468255291

TLR ligand: TLR

--

e5

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

--

p3 p4 p5

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
330.3709262766688, 600.0037870901433
325.2953181621842, 295.00711349159013

--

e50

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelopeLumen

--

--

--

true true true true

csml-variable:Double

m50

0

false

infinite

0

unit false true false

--

Go back
365.5052436945582, 606.9950268070094
190.2099253313331, 285.92065209041164

--

e51

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearPore

--

--

--

true true true true

csml-variable:Double

m51

0

false

infinite

0

unit false true false

--

Go back
334.61127493055204, 603.9412536973206
316.814620854418, 287.13218027723536

--

e52

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearInnerMembrane

--

--

--

true true true true

csml-variable:Double

m52

0

false

infinite

0

unit false true false

--

Go back
335.21703902396393, 604.5470177907324
315.603092667594, 285.92065209041164

--

e53

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearLumen

--

--

--

true true true true

csml-variable:Double

m53

0

false

infinite

0

unit false true false

--

Go back
330.3709262766688, 600.0037870901433
325.2953181621842, 295.00711349159013

--

e54

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearOuterMembrane

--

--

--

true true true true

csml-variable:Double

m54

0

false

infinite

0

unit false true false

--

Go back
330.3709262766688, 600.0037870901433
325.2953181621842, 295.00711349159013

--

e55

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleus

--

--

--

true true true true

csml-variable:Double

m55

0

false

infinite

0

unit false true false

--

Go back
335.21703902396393, 604.5470177907324
315.603092667594, 285.92065209041164

--

e56

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleoplasm

--

--

--

true true true true

csml-variable:Double

m56

0

false

infinite

0

unit false true false

--

Go back
567.830450894129, 721.1566057725213
20.322664142322413, 18.397359118312952

--

e57

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearBody

--

--

--

true true true true

csml-variable:Double

m57

0

false

infinite

0

unit false true false

--

Go back
514.5232106738831, 805.9635788501855
57.54758887412939, 52.09571203342251

--

e58

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleolus

--

--

--

true true true true

csml-variable:Double

m58

0

false

infinite

0

unit false true false

--

Go back
330.3709262766688, 600.0037870901433
325.2953181621842, 295.00711349159013

--

e59

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelope

--

--

--

true true true true

csml-variable:Double

m59

0

false

infinite

0

unit false true false

--

Go back
394.0, 704.0
43.910034602076124, 23.418685121107266

cytokine

--

e6

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p3 p11

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
407.04120245672334, 731.1025106619593
10.301624754934286, 4.960041548672069

--

e60

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Chromatin

--

--

--

true true true true

csml-variable:Double

m60

0

false

infinite

0

unit false true false

--

Go back
406.6972020465667, 716.310493025226
35.26004204105049, 63.4680756738909

--

e61

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearChromosome

--

--

--

true true true true

csml-variable:Double

m61

0

false

infinite

0

unit false true false

--

Go back
421.48921968330035, 757.5905422440171
5.504006562505436, 5.504006562505442

--

e62

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearCentromere

--

--

--

true true true true

csml-variable:Double

m62

0

false

infinite

0

unit false true false

--

Go back
211.6117817289301, 102.61254639608437
586.6168969647762, 831.2209905331147

--

e7

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell

--

--

--

true true true true

csml-variable:Double

m7

0

false

infinite

0

unit false true false

--

Go back
213.7075313385961, 117.28279366374625
562.7485792505491, 817.1109370717977

--

e8

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell_WithoutCellWall_

--

--

--

true true true true

csml-variable:Double

m8

0

false

infinite

0

unit false true false

--

Go back
219.296196964372, 131.95304093140808
560.1793232993199, 806.394731881576

--

e9

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytoplasm

--

--

--

true true true true

csml-variable:Double

m9

0

false

infinite

0

unit false true false

--

Go back
129.0, 761.0
30.0, 30.0

p1

p1

cso30:i:CE_CellDifferentiation

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c12 : 1
stoichiometry:c13 : 1

m3957*m93228*m11*0.1

nodelay

--

true

0

false

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).

Go back
548.0, 102.0
24.0, 24.0

p10

p10

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c24 : 1
stoichiometry:c25 : 1
stoichiometry:c26 : 1

m119368*m36179*0.1

nodelay

--

true

0

false

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.

Go back
311.0, 659.0
25.0, 25.0

p11

p11

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c27 : 1
stoichiometry:c29 : 1
stoichiometry:c28 : 1

m6*m19314*0.1

nodelay

--

true

0

false

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.

Go back
447.0, 55.0
25.0, 25.0

p2

p2

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c2 : 1
stoichiometry:c3 : 1
stoichiometry:c4 : 1

m3965*m119368*0.1

nodelay

--

true

0

false

PMID: 15886091, 11607032 TLR3 is an endosomal Toll-like receptor that recognizes double-stranded (ds) RNA [11], a by-product of most viral infections.

Go back
312.0, 704.0
23.0, 23.0

p3

p3

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c6 : 1
stoichiometry:c7 : 1
stoichiometry:c5 : 1

m6*m5*0.1

nodelay

--

true

0

false

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).

Go back
454.0, 690.0
27.0, 27.0

p4

p4

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c8 : 1

m5*0.1

nodelay

--

true

0

false

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).

Go back
510.0, 694.0
27.0, 27.0

p5

p5

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c11 : 1
stoichiometry:c9 : 1

m5*0.1

nodelay

--

true

0

false

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).

Go back
446.0, 222.0
27.0, 27.0

p6

p6

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c14 : 1
stoichiometry:c16 : 1
stoichiometry:c15 : 1

m12*m19314*0.1

nodelay

--

true

0

false

PMID: 15886091 The viral dsRNA contained within the apoptotic bodies is recognized by endosomal TLR3, inducing NFkappaB activation and DC maturation.

Go back
149.0, 225.0
30.0, 30.0

p7

p7

cso30:i:CE_CellDifferentiation

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c17 : 1
stoichiometry:c20 : 1

m19314*m1634*0.1

nodelay

--

true

0

false

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.

Go back
511.0, 503.0
25.0, 25.0

p8

p8

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c18 : 1
stoichiometry:c19 : 1

m14*0.1

nodelay

--

true

0

false

PMID: 15886091 DC maturation and cross-priming can be enhanced by type I IFN released by infected cells.

Go back
328.0, 106.0
24.0, 24.0

p9

p9

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c21 : 1
stoichiometry:c22 : 1
stoichiometry:c23 : 1

m119368*m1055*0.1

nodelay

--

true

0

false

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.

Go back
144.0, 730.0

c1

c1

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
488.67753856832496, 618.0

c10

c10

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
544.4906334205524, 619.0

c11

c11

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
166.9776955521664, 777.5969704154683

c12

c12

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
166.99334442480463, 761.0

c13

c13

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
480.99451867013414, 234.0

c14

c14

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
473.0, 248.0

c15

c15

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
460.0, 132.0

c16

c16

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
186.9999797893248, 132.0

c17

c17

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
524.0, 536.0

c18

c18

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
187.0, 516.0

c19

c19

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
411.0, 85.49298826370973

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
164.0, 263.0

c20

c20

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
358.18872400215145, 31.0

c21

c21

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
340.0, 138.0

c22

c22

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
297.65685424949237, 130.0

c23

c23

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
474.0, 33.0

c24

c24

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
560.0, 134.0

c25

c25

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
572.0, 125.0

c26

c26

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
343.2044130909166, 681.4779925266494

c27

c27

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
165.7641158667119, 675.0

c28

c28

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
328.9020981508355, 132.0

c29

c29

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
460.0, 34.0

c3

c3

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
460.0, 80.0

c4

c4

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
166.0, 716.0

c5

c5

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
343.0, 716.0

c6

c6

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
342.800342728028, 616.0

c7

c7

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
468.0, 717.0

c8

c8

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
524.0, 721.0

c9

c9

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back