_enti_e7
_enti_e8
_enti_e1
_enti_e9
_enti_e10
_enti_e4
_enti_e2
_enti_e3
_enti_e55
_enti_e53
_enti_e59
_enti_e54
_enti_e50
_enti_e51
_enti_e56
_enti_e52
_enti_e57
_enti_e61
_enti_e58
_enti_e62
_enti_e60
g2_fact_g2
g1_fact_g14
g1_fact_g1
g2_fact_g12
g2_fact_g13
p1_propro_p1
PMID: 18406367, 16506285
activation of TLR4 by S-form LPS requires the cooperation of accessory proteins (CD14, LBP), while R-form LPS can trigger the TLR4/MD-2 directly.
c1 cso30:c:InputProcess connector
c3 cso30:c:InputProcess connector
c2 cso30:c:OutputProcess connector
p2_propro_p2
PMID: 18406367, 16506285
activation of TLR4 by S-form LPS requires the cooperation of accessory proteins (CD14, LBP), while R-form LPS can trigger the TLR4/MD-2 directly.
c4 cso30:c:InputProcess connector
c5 cso30:c:InputProcess connector
c6 cso30:c:OutputProcess connector
p3_propro_p3
PMID: 18406367, 11500507, 17803912
In this function, TLR4 is aided by the LPS recognition protein MD (myeloid differentiation protein)-2.
c7 cso30:c:InputProcess connector
c8 cso30:c:InputProcess connector
c9 cso30:c:OutputProcess connector
p4_propro_p4
PMID: 18406367, 15608698, 2402637, 1698311
The activation of TLR4 is assisted further by the plasma protein LBP (LPS-binding protein).
PMID: 18406367
According to the current consensus, recognition of LPS by cells of the innate immune system proceeds via the LPS receptor complex, which, in addition to the signaling subunit TLR4, consists of recognition subunits MD-2 and glycosyl-phosphatidylinositol-anchored CD14 (mCD14).
c10 cso30:c:InputProcess connector
c11 cso30:c:InputProcess connector
c12 cso30:c:OutputProcess connector
p5_propro_p5
PMID: 18406367, 16506285
activation of TLR4 by S-form LPS requires the cooperation of accessory proteins (CD14, LBP), while R-form LPS can trigger the TLR4/MD-2 directly.
c13 cso30:c:InputProcess connector
c14 cso30:c:InputProcess connector
c15 cso30:c:OutputProcess connector
p6_propro_p6
PMID: 18406367, 6714230, 324763
Furthermore, while cells (e.g., macrophages and B cells) carrying murine or human TLR4 can be stimulated with lipid A, only those carrying the murine receptor respond to the lipid A precursor (tetra-acylated lipid A).
c16 cso30:c:InputProcess connector
c17 cso30:c:InputProcess connector
c18 cso30:c:OutputProcess connector
p7_propro_p7
PMID: 18406367, 9755338, 9620656
The induction of IFN-gamma is complex. Induction by bacteria is dependent on interleukin (IL)-12 and IL-18.
c20 cso30:c:InputProcess connector
c19 cso30:c:InputProcess connector
c21 cso30:c:OutputProcess connector
p8_propro_p8
PMID: 18406367, 12165484
In addition to the IL-12-dependent pathway, we reported the existence of a further, IL-12-independent pathway of IFN-gamma induction based on activation of the signal transducer and activator of transcription (STAT)4 by IFN-alpha/beta and IL-18 signaling.
c23 cso30:c:InputProcess connector
c22 cso30:c:InputProcess connector
c24 cso30:c:OutputProcess connector
p9_propro_p9
PMID: 18406367, 9755338, 9620656
The induction of IFN-gamma is complex. Induction by bacteria is dependent on interleukin (IL)-12 and IL-18.
c25 cso30:c:InputAssociation connector
c26 cso30:c:OutputProcess connector
p10_propro_p10
PMID: 18406367, 12165484
In addition to the IL-12-dependent pathway, we reported the existence of a further, IL-12-independent pathway of IFN-gamma induction based on activation of the signal transducer and activator of transcription (STAT)4 by IFN-alpha/beta and IL-18 signaling.
c27 cso30:c:InputProcess connector
c32 cso30:c:InputProcess connector
c28 cso30:c:OutputProcess connector
p11_propro_p11
PMID: 18406367, 12165484
In addition to the IL-12-dependent pathway, we reported the existence of a further, IL-12-independent pathway of IFN-gamma induction based on activation of the signal transducer and activator of transcription (STAT)4 by IFN-alpha/beta and IL-18 signaling.
c29 cso30:c:InputProcess connector
c31 cso30:c:InputAssociation connector
c30 cso30:c:OutputProcess connector
p12_propro_p12
PMID: 18406367, 12165484
In addition to the IL-12-dependent pathway, we reported the existence of a further, IL-12-independent pathway of IFN-gamma induction based on activation of the signal transducer and activator of transcription (STAT)4 by IFN-alpha/beta and IL-18 signaling.
c33 cso30:c:InputAssociation connector
c34 cso30:c:OutputProcess connector
p13_propro_p13
PMID: 18406367, 12872135, 16924467
LPS induction of pro-inflammatory cytokines, such as TNF-alpha or IL-6 via TLR4 requires the assistance of the adapter proteins MyD88 and TRIF, in association with Mal and TRAM, respectively, whereby the induction of IFN-alpha/beta is MyD88/Mal independent.
c36 cso30:c:InputProcess connector
c37 cso30:c:InputProcess connector
c35 cso30:c:InputProcess connector
c38 cso30:c:OutputProcess connector
p14_propro_p14
PMID: 18406367, 12872135, 16924467
LPS induction of pro-inflammatory cytokines, such as TNF-alpha or IL-6 via TLR4 requires the assistance of the adapter proteins MyD88 and TRIF, in association with Mal and TRAM, respectively, whereby the induction of IFN-alpha/beta is MyD88/Mal independent.
c39 cso30:c:InputProcess connector
c40 cso30:c:InputProcess connector
c42 cso30:c:InputProcess connector
c41 cso30:c:OutputProcess connector
p15_propro_p15
PMID: 18406367, 12872135, 16924467
LPS induction of pro-inflammatory cytokines, such as TNF-alpha or IL-6 via TLR4 requires the assistance of the adapter proteins MyD88 and TRIF, in association with Mal and TRAM, respectively, whereby the induction of IFN-alpha/beta is MyD88/Mal independent.
c45 cso30:c:InputAssociation connector
c43 cso30:c:OutputProcess connector
p16_propro_p16
PMID: 18406367, 12872135, 16924467
LPS induction of pro-inflammatory cytokines, such as TNF-alpha or IL-6 via TLR4 requires the assistance of the adapter proteins MyD88 and TRIF, in association with Mal and TRAM, respectively, whereby the induction of IFN-alpha/beta is MyD88/Mal independent.
c46 cso30:c:InputAssociation connector
c44 cso30:c:OutputProcess connector
p17_propro_p17
PMID: 18406367, 12872135, 16924467
LPS induction of pro-inflammatory cytokines, such as TNF-alpha or IL-6 via TLR4 requires the assistance of the adapter proteins MyD88 and TRIF, in association with Mal and TRAM, respectively, whereby the induction of IFN-alpha/beta is MyD88/Mal independent.
c48 cso30:c:InputAssociation connector
c50 cso30:c:OutputProcess connector
p18_propro_p18
PMID: 18406367, 12872135, 16924467
LPS induction of pro-inflammatory cytokines, such as TNF-alpha or IL-6 via TLR4 requires the assistance of the adapter proteins MyD88 and TRIF, in association with Mal and TRAM, respectively, whereby the induction of IFN-alpha/beta is MyD88/Mal independent.
c47 cso30:c:InputAssociation connector
c49 cso30:c:OutputProcess connector
p19_propro_p19
PMID: 18406367, 16924467
LP, depending on their chemical structure, are ligands of the heterodimeric surface receptors TLR2/TLR6 or TLR2/TLR1.
c51 cso30:c:InputProcess connector
c52 cso30:c:InputProcess connector
c62 cso30:c:OutputProcess connector
p20_propro_p20
PMID: 18406367, 10549626, 10588727
The cytokine responses to S. aureus were suggested earlier to be TLR2 dependent, since peptidoglycan and lipoteichoic acid isolated from this micro-organism were shown to trigger this receptor.
c53 cso30:c:InputProcess connector
c54 cso30:c:InputProcess connector
c63 cso30:c:OutputProcess connector
p21_propro_p21
PMID: 18406367, 16924467
LP, depending on their chemical structure, are ligands of the heterodimeric surface receptors TLR2/TLR6 or TLR2/TLR1.
c55 cso30:c:InputProcess connector
c56 cso30:c:InputProcess connector
c65 cso30:c:OutputProcess connector
p22_propro_p22
PMID: 18406367, 10549626, 10588727
The cytokine responses to S. aureus were suggested earlier to be TLR2 dependent, since peptidoglycan and lipoteichoic acid isolated from this micro-organism were shown to trigger this receptor.
c59 cso30:c:InputProcess connector
c67 cso30:c:InputProcess connector
c68 cso30:c:OutputProcess connector
p23_propro_p23
PMID: 18406367, 10549626, 10588727
The cytokine responses to S. aureus were suggested earlier to be TLR2 dependent, since peptidoglycan and lipoteichoic acid isolated from this micro-organism were shown to trigger this receptor.
c57 cso30:c:InputProcess connector
c58 cso30:c:InputProcess connector
c66 cso30:c:OutputProcess connector
p24_propro_p24
PMID: 18406367, 10549626, 10588727
The cytokine responses to S. aureus were suggested earlier to be TLR2 dependent, since peptidoglycan and lipoteichoic acid isolated from this micro-organism were shown to trigger this receptor.
c60 cso30:c:InputProcess connector
c61 cso30:c:InputProcess connector
c64 cso30:c:OutputProcess connector
p25_propro_p25
PMID: 18406367
Since TRIF function is absolutely necessary for TLR3 signaling, our findings indicate that the role of TLR3 in the recognition of dsRNA had been overestimated in the past.
c69 cso30:c:InputProcess connector
c74 cso30:c:InputProcess connector
c70 cso30:c:OutputProcess connector
p26_propro_p26
PMID: 18406367
Since TRIF function is absolutely necessary for TLR3 signaling, our findings indicate that the role of TLR3 in the recognition of dsRNA had been overestimated in the past.
c71 cso30:c:InputProcess connector
c73 cso30:c:InputProcess connector
c72 cso30:c:OutputProcess connector
p27_propro_p27
PMID: 18406367
priming with P. acnes enhanced only moderately the TNF-alpha and IL-6 responses to dsRNA and caused no enhancement of the IFN-alpha/beta response.
c78 cso30:c:InputAssociation connector
c76 cso30:c:OutputProcess connector
p28_propro_p28
PMID: 18406367
priming with P. acnes enhanced only moderately the TNF-alpha and IL-6 responses to dsRNA and caused no enhancement of the IFN-alpha/beta response.
c77 cso30:c:InputAssociation connector
c75 cso30:c:OutputProcess connector
p29_propro_p29
PMID: 184066367, 16730994
the cytoplasmic melanoma differentiation-associated gene-5 (mda-5) is the dominant receptor mediating the IFN-alpha/beta responses to dsRNA.
c84 cso30:c:InputAssociation connector
c79 cso30:c:OutputProcess connector
p30_propro_p30
PMID: 184066367, 16730994
the cytoplasmic melanoma differentiation-associated gene-5 (mda-5) is the dominant receptor mediating the IFN-alpha/beta responses to dsRNA.
c85 cso30:c:InputAssociation connector
c80 cso30:c:OutputProcess connector
p31_propro_p31
PMID: 184066367, 16730994
the cytoplasmic melanoma differentiation-associated gene-5 (mda-5) is the dominant receptor mediating the IFN-alpha/beta responses to dsRNA.
c81 cso30:c:InputProcess connector
c82 cso30:c:InputProcess connector
c83 cso30:c:OutputProcess connector
p32_propro_p32
PMID: 18406367
induction of mRNA for IL-12p40, IL-12p35, IL-12Rbeta1 and IL-12Rbeta2 was also absent in the liver of TLR9/ mice, 3 days after P. acnes treatment.
c86 cso30:c:InputProcess connector
c87 cso30:c:InputProcess connector
c88 cso30:c:OutputProcess connector
p33_propro_p33
PMID: 18406367
induction of mRNA for IL-12p40, IL-12p35, IL-12Rbeta1 and IL-12Rbeta2 was also absent in the liver of TLR9/ mice, 3 days after P. acnes treatment.
c93 cso30:c:InputAssociation connector
c89 cso30:c:OutputProcess connector
p34_propro_p34
PMID: 18406367
induction of mRNA for IL-12p40, IL-12p35, IL-12Rbeta1 and IL-12Rbeta2 was also absent in the liver of TLR9/ mice, 3 days after P. acnes treatment.
c94 cso30:c:InputAssociation connector
c90 cso30:c:OutputProcess connector
p35_propro_p35
PMID: 18406367
induction of mRNA for IL-12p40, IL-12p35, IL-12Rbeta1 and IL-12Rbeta2 was also absent in the liver of TLR9/ mice, 3 days after P. acnes treatment.
c95 cso30:c:InputAssociation connector
c91 cso30:c:OutputProcess connector
p36_propro_p36
PMID: 18406367
induction of mRNA for IL-12p40, IL-12p35, IL-12Rbeta1 and IL-12Rbeta2 was also absent in the liver of TLR9/ mice, 3 days after P. acnes treatment.
c96 cso30:c:InputAssociation connector
c92 cso30:c:OutputProcess connector
R form-LPS_enti_e5
R form-LPS
S form-LPS_enti_e6
S form-LPS
S form-LPS:LBP_enti_MO000021928
S form-LPS:LBP
S-formLPS:LBP:CD14_enti_MO000021929
S-formLPS:LBP:CD14
LBP_enti_MO000019420
LBP
CD14_enti_MO000018132
CD14
TLR4_enti_MO000019394
TLR4
MD-2_enti_MO000022131
MD-2
TLR4: MD-2_enti_e11
TLR4: MD-2
S form-LPS:LBP:CD14: TLR4: MD-2_enti_e12
S form-LPS:LBP:CD14: TLR4: MD-2
R form-LPS: TLR4: MD-2_enti_e13
R form-LPS: TLR4: MD-2
lipid A_enti_e14
lipid A
lipid A: TLR4: MD-2_enti_e15
lipid A: TLR4: MD-2
IL-12_enti_MO000017265
IL-12
IL-18_enti_MO000016625
IL-18
STAT4_enti_MO000017181
STAT4
IFN-gamma_enti_G010453
IFN-gamma
IL-12 : IL-12R_enti_e17
IL-12 : IL-12R
IFNalpha, IFNbeta_enti_MO000038482
IFNalpha, IFNbeta
IL-18: IL-18R_enti_e19
IL-18: IL-18R
STAT4 {activated}_enti_e20
STAT4 {activated}
IFNalpha, IFNbeta [activated}_enti_e21
IFNalpha, IFNbeta [activated}
TRIF_enti_MO000041125
TRIF
MyD88_enti_MO000016573
MyD88
S form-LPS:LBP:CD14: TLR4: MD-2: MyD88: MAL_enti_e22
S form-LPS:LBP:CD14: TLR4: MD-2: MyD88: MAL
TRAM_enti_MO000041132
TRAM
S form-LPS:LBP:CD14: TLR4: MD-2: TRIF: TRAM_enti_e23
S form-LPS:LBP:CD14: TLR4: MD-2: TRIF: TRAM
MAL_enti_MO000068831
MAL
TNF-alpha_enti_G010329
TNF-alpha
IL-6_enti_G010262
IL-6
IFN-alpha_enti_e24
IFN-alpha
IFN-beta_enti_G010228
IFN-beta
TLR2:TLR1_enti_e25
TLR2:TLR1
TLR2: TLR6_enti_e26
TLR2: TLR6
PGN_enti_MO000042032
PGN
LTA_enti_e28
LTA
LP: TLR2:TLR1_enti_e29
LP: TLR2:TLR1
PGN: TLR2:TLR1_enti_e30
PGN: TLR2:TLR1
LTA: TLR2:TLR1_enti_e31
LTA: TLR2:TLR1
LP: TLR2: TLR6_enti_e32
LP: TLR2: TLR6
PGN: TLR2: TLR6_enti_e33
PGN: TLR2: TLR6
LTA: TLR2: TLR6_enti_e34
LTA: TLR2: TLR6
TLR3_enti_MO000019398
TLR3
dsRNA:TLR3:TRIF_enti_MO000041437
dsRNA:TLR3:TRIF
dsRNA:TLR3_enti_MO000041446
dsRNA:TLR3
dsRNA_enti_MO000022224
dsRNA
mda-5_enti_MO000103999
mda-5
dsRNA: mda-5_enti_e35
dsRNA: mda-5
TLR9_enti_MO000042012
TLR9
TLR9 ligand_enti_e36
TLR9 ligand
TLR9 ligand: TLR9_enti_e37
TLR9 ligand: TLR9
IL-12 p40_enti_G010657
IL-12 p40
IL-12p35_enti_e38
IL-12p35
IL-12Rbeta1_enti_e39
IL-12Rbeta1
IL-12Rbeta2_enti_e40
IL-12Rbeta2
IL-12R_enti_MO000033676
IL-12R
IL-18R_enti_e16
IL-18R
LP_enti_e18
LP