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PMID: 18054516 TLR4 (together with its soluble coreceptor MD-2) binds Gram (−) bacteria-derived LPS

PMID: 18054516 TLR2 recognizes peptidoglycan and lipopeptides

PMID: 18054516 TLR2 recognizes peptidoglycan and lipopeptides

PMID: 18054516 TLR5 recognizes flagellin

PMID: 18054516, 14976261, 14976262 TLR7 and TLR8 recognize single-strand (ss)RNA and are also activated by infections with ssRNA viruses, including influenza virus and vesicular stomatitis virus

PMID: 18054516, 14976261, 14976262 TLR7 and TLR8 recognize single-strand (ss)RNA and are also activated by infections with ssRNA viruses, including influenza virus and vesicular stomatitis virus

PMID: 18054516 TLR3 is triggered by double-strand (ds)RNA.

PMID: 18054516 TLR9 is known to bind unmethylated bacterial and viral dsDNA

PMID: 18054516, 11544529, 16410796 With the exception of TLR3, which signals solely by TRIF, all TLRs recruit MyD88, which triggers signalling pathways leading to nuclear translocation of NF-κB

PMID: 18054516, 16410796, 11544529 In the case of TLR4, another adaptor molecule, TRAM, is required to recruit TRIF to TLR4 and, in turn, to induce the pathway leading to the IFN-β expression

PMID: 18054516, 11812998, 12032557, 15661881 In addition to ssRNA, the synthetic imidazoquinoline, imiquimod, a low molecular weight immune response modifier, activates TLR7 in both humans and mice while its derivative resiquimod (R-848) activates TLR7 and TLR8 in humans, but only TLR7 in mice

PMID: 18054516, 11812998, 12032557, 15661881 In addition to ssRNA, the synthetic imidazoquinoline, imiquimod, a low molecular weight immune response modifier, activates TLR7 in both humans and mice while its derivative resiquimod (R-848) activates TLR7 and TLR8 in humans, but only TLR7 in mice

PMID: 18054516, 11812998, 12032557, 15661881 In addition to ssRNA, the synthetic imidazoquinoline, imiquimod, a low molecular weight immune response modifier, activates TLR7 in both humans and mice while its derivative resiquimod (R-848) activates TLR7 and TLR8 in humans, but only TLR7 in mice

PMID: 18054516, 11544529, 17048703 With the exception of TLR3, which signals solely by TRIF, all TLRs recruit MyD88, which triggers signalling pathways leading to nuclear translocation of NF-κB

PMID: 18054516, 11544529, 17048703 With the exception of TLR3, which signals solely by TRIF, all TLRs recruit MyD88, which triggers signalling pathways leading to nuclear translocation of NF-κB

PMID: 18054516, 11544529, 17048703 With the exception of TLR3, which signals solely by TRIF, all TLRs recruit MyD88, which triggers signalling pathways leading to nuclear translocation of NF-κB

PMID: 18054516, 11544529, 17048703 With the exception of TLR3, which signals solely by TRIF, all TLRs recruit MyD88, which triggers signalling pathways leading to nuclear translocation of NF-κB

PMID: 18054516, 11544529, 17048703 With the exception of TLR3, which signals solely by TRIF, all TLRs recruit MyD88, which triggers signalling pathways leading to nuclear translocation of NF-κB

PMID: 18054516, 11544529, 17048703 With the exception of TLR3, which signals solely by TRIF, all TLRs recruit MyD88, which triggers signalling pathways leading to nuclear translocation of NF-κB

indirect

PMID: 18054516, 12702806, 14517278 This pathway mainly mediates the phosphorylation-induced activation of IRF-3 by two IkB kinase-related kinases, inhibitory protein kB kinase (IKK)-var epsilon and TANK binding kinase (TBK)1

indirect

PMID: 18054516, 12702806, 14517278 This pathway mainly mediates the phosphorylation-induced activation of IRF-3 by two IkB kinase-related kinases, inhibitory protein kB kinase (IKK)-var epsilon and TANK binding kinase (TBK)1

PMID: 18054516, 12702806, 14517278 This pathway mainly mediates the phosphorylation-induced activation of IRF-3 by two IkB kinase-related kinases, inhibitory protein kB kinase (IKK)-var epsilon and TANK binding kinase (TBK)1

PMID: 18054516, 16214811, 12821121 Recent reports have also shown that IRF-7 can be directly activated by TLR4 and TLR3 in IRF-3-deficient DC indicating that IRF-7 may potentiate the IRF-3-dependent induction of IFN-β PMID: 18054516, 9786932, 9877175 Similar to IRF-3, IRF-7 undergoes serine phosphorylation by IKK-var epsilon and TBK1 followed by nuclear translocation PMID: 18054516, 16964262 Carty et al. recently demonstrated that a TIR adaptor SARM inhibits TRIF-induced IRF-7 activation in TLR3 or TLR4-stimulated cells

PMID: 18054516, 9786932, 9877175 Similar to IRF-3, IRF-7 undergoes serine phosphorylation by IKK-var epsilon and TBK1 followed by nuclear translocation

PMID: 18054516, 9786932, 9877175 Similar to IRF-3, IRF-7 undergoes serine phosphorylation by IKK-var epsilon and TBK1 followed by nuclear translocation

PMID: 18054516, 3329166, 16932750, 16979567 These events result in the assembly of the enhanceosome, a multiprotein complex consisting of ATF2/c-Jun, IRF-3/IRF-7, and NF-κB, all of which are required for the transcription of the IFN-β gene

PMID: 18054516, 3329166, 16932750, 16979567 These events result in the assembly of the enhanceosome, a multiprotein complex consisting of ATF2/c-Jun, IRF-3/IRF-7, and NF-κB, all of which are required for the transcription of the IFN-β gene PMID: 18054516, 12077266, 14991609 In particular, the stimulation of TLR3 and TLR4 is associated mainly with the release of IFN-β and a poor production of IFN-α1 from human myeloid DC PMID: 18054516, 12077266, 14991609, 16846591 In myeloid DC the activation of IRF-3 following TLR3 or TLR4 triggering is responsible for the selective expression of IFN-β and IFN-α1 which contain in their promoter specific sequences recognizing this transcription factor

indirect

PMID: 18054516, 11544529, 17048703 With the exception of TLR3, which signals solely by TRIF, all TLRs recruit MyD88, which triggers signalling pathways leading to nuclear translocation of NF-κB

indirect

PMID: 18054516, 11544529, 17048703 With the exception of TLR3, which signals solely by TRIF, all TLRs recruit MyD88, which triggers signalling pathways leading to nuclear translocation of NF-κB

indirect

PMID: 18054516, 11544529, 17048703 With the exception of TLR3, which signals solely by TRIF, all TLRs recruit MyD88, which triggers signalling pathways leading to nuclear translocation of NF-κB

indirect

PMID: 18054516, 11544529, 17048703 With the exception of TLR3, which signals solely by TRIF, all TLRs recruit MyD88, which triggers signalling pathways leading to nuclear translocation of NF-κB

indirect

PMID: 18054516, 11544529, 17048703 With the exception of TLR3, which signals solely by TRIF, all TLRs recruit MyD88, which triggers signalling pathways leading to nuclear translocation of NF-κB

indirect

PMID: 18054516, 11544529, 17048703 With the exception of TLR3, which signals solely by TRIF, all TLRs recruit MyD88, which triggers signalling pathways leading to nuclear translocation of NF-κB

indirect

PMID: 18054516, 9822609 While IRF-3 is constitutively expressed, IRF-7 expression is induced by IFN-α/β through the activation of IFN-stimulated gene factor (ISGF)-3

indirect

PMID: 18054516, 9822609 While IRF-3 is constitutively expressed, IRF-7 expression is induced by IFN-α/β through the activation of IFN-stimulated gene factor (ISGF)-3

PMID: 18054516, 16699525 The peptidyl prolyl isomerase Pin1 interacts with IRF-3 in the nucleus and facilitates the conjugation of polyubiquitin and the proteasome-dependent degradation of IRF-3, thereby blocking the IFN-β production downstream of TLR3, TLR4 and RIG-I pathways

PMID: 18054516, 16699525 The peptidyl prolyl isomerase Pin1 interacts with IRF-3 in the nucleus and facilitates the conjugation of polyubiquitin and the proteasome-dependent degradation of IRF-3, thereby blocking the IFN-β production downstream of TLR3, TLR4 and RIG-I pathways

PMID: 18054516, 16699525 The peptidyl prolyl isomerase Pin1 interacts with IRF-3 in the nucleus and facilitates the conjugation of polyubiquitin and the proteasome-dependent degradation of IRF-3, thereby blocking the IFN-β production downstream of TLR3, TLR4 and RIG-I pathways

PMID: 18054516 Suppressor IKKvar epsilon (SIKE) is a suppressor that interacts with both TBK1 and IKKvar epsilon and sequester them in inactive complex.

indirect

PMID: 18054516 Upon viral infection or TLR3 triggering, SIKE dissociates from TBK1 and IKKvar epsilon allowing type I IFN gene expression.

PMID: 18054516, 10817963 Once secreted from infected cells, IFNs induce in an autocrine and paracrine fashion the activation of Janus kinases (JAKs) and STAT transcription factors, leading to expression of IFN-stimulated genes (ISGs)

PMID: 18054516, 10817963 Once secreted from infected cells, IFNs induce in an autocrine and paracrine fashion the activation of Janus kinases (JAKs) and STAT transcription factors, leading to expression of IFN-stimulated genes (ISGs)

PMID: 18054516, 10817963 Once secreted from infected cells, IFNs induce in an autocrine and paracrine fashion the activation of Janus kinases (JAKs) and STAT transcription factors, leading to expression of IFN-stimulated genes (ISGs) PMID: 18054516 Upon phosphorylation and translocation into the nucleus, STAT bind as STAT-1 homodimer (GAF, IFN-γ activated factor) to STAT binding element (SBE) or as heterotrimeric ISGF-3 complex (consisting of IRF-9, STAT-1 and STAT-2) to the IFN-stimulated response element (ISRE) in the promoter of target genes.

PMID: 18054516 Upon phosphorylation and translocation into the nucleus, STAT bind as STAT-1 homodimer (GAF, IFN-γ activated factor) to STAT binding element (SBE) or as heterotrimeric ISGF-3 complex (consisting of IRF-9, STAT-1 and STAT-2) to the IFN-stimulated response element (ISRE) in the promoter of target genes.

PMID: 18054516 Upon phosphorylation and translocation into the nucleus, STAT bind as STAT-1 homodimer (GAF, IFN-γ activated factor) to STAT binding element (SBE) or as heterotrimeric ISGF-3 complex (consisting of IRF-9, STAT-1 and STAT-2) to the IFN-stimulated response element (ISRE) in the promoter of target genes.

PMID: 18054516 Upon phosphorylation and translocation into the nucleus, STAT bind as STAT-1 homodimer (GAF, IFN-γ activated factor) to STAT binding element (SBE) or as heterotrimeric ISGF-3 complex (consisting of IRF-9, STAT-1 and STAT-2) to the IFN-stimulated response element (ISRE) in the promoter of target genes.

PMID: 18054516 Upon phosphorylation and translocation into the nucleus, STAT bind as STAT-1 homodimer (GAF, IFN-γ activated factor) to STAT binding element (SBE) or as heterotrimeric ISGF-3 complex (consisting of IRF-9, STAT-1 and STAT-2) to the IFN-stimulated response element (ISRE) in the promoter of target genes.

PMID: 18054516, 9822609 While IRF-3 is constitutively expressed, IRF-7 expression is induced by IFN-α/β through the activation of IFN-stimulated gene factor (ISGF)-3 PMID: 18054516 Among these, IRF-1 and IRF-7 are transcriptionally regulated by SBE and ISRE sites present within their respective promoters

PMID: 18054516 Among these, IRF-1 and IRF-7 are transcriptionally regulated by SBE and ISRE sites present within their respective promoters.

PMID: 18054516, 12077266, 14991609 In particular, the stimulation of TLR3 and TLR4 is associated mainly with the release of IFN-β and a poor production of IFN-α1 from human myeloid DC PMID: 18054516, 12077266, 14991609, 16846591 In myeloid DC the activation of IRF-3 following TLR3 or TLR4 triggering is responsible for the selective expression of IFN-β and IFN-α1 which contain in their promoter specific sequences recognizing this transcription factor

PMID: 18054516, 12077266, 14991609 In particular, the stimulation of TLR3 and TLR4 is associated mainly with the release of IFN-β and a poor production of IFN-α1 from human myeloid DC PMID: 18054516, 12077266, 14991609, 16846591 In myeloid DC the activation of IRF-3 following TLR3 or TLR4 triggering is responsible for the selective expression of IFN-β and IFN-α1 which contain in their promoter specific sequences recognizing this transcription factor

PMID: 18054516, 12077266, 14991609 In particular, the stimulation of TLR3 and TLR4 is associated mainly with the release of IFN-β and a poor production of IFN-α1 from human myeloid DC PMID: 18054516, 12077266, 14991609, 16846591 In myeloid DC the activation of IRF-3 following TLR3 or TLR4 triggering is responsible for the selective expression of IFN-β and IFN-α1 which contain in their promoter specific sequences recognizing this transcription factor

PMID: 18054516 During a viral infection, RIG-1 and MDA5 are activated upon detection of dsRNA by the RNA helicase domain, and trigger the activation of NF-κB and IRF3/7, which cooperate in the induction of type I IFNs

PMID: 18054516 During a viral infection, RIG-1 and MDA5 are activated upon detection of dsRNA by the RNA helicase domain, and trigger the activation of NF-κB and IRF3/7, which cooperate in the induction of type I IFNs

PMID: 18054516, 16177806, 16125763, 16127453, 16039576 It has been proposed that once activated by dsRNA, RIG-I interacts with IPS-1 via their respective CARD domains, resulting in the recruitment of appropriate signalling intermediates, such as IKKs for NF-κB and IRF activation

PMID: 18054516, 16177806, 16125763, 16127453, 16039576 It has been proposed that once activated by dsRNA, RIG-I interacts with IPS-1 via their respective CARD domains, resulting in the recruitment of appropriate signalling intermediates, such as IKKs for NF-κB and IRF activation

indirect

PMID: 18054516, 16177806, 16125763, 16127453, 16039576 It has been proposed that once activated by dsRNA, RIG-I interacts with IPS-1 via their respective CARD domains, resulting in the recruitment of appropriate signalling intermediates, such as IKKs for NF-κB and IRF activation

indirect

PMID: 18054516, 16177806, 16125763, 16127453, 16039576 It has been proposed that once activated by dsRNA, RIG-I interacts with IPS-1 via their respective CARD domains, resulting in the recruitment of appropriate signalling intermediates, such as IKKs for NF-κB and IRF activation

PMID: 18054516, 17618271 The very recent identification of DNA-dependent activator of IRF (DAI) as a cytosolic DNA sensor able to induce type I IFN expression following the recognition of different sources of microbial DNA, provides an explanation of how different pathogens may induce type I IFN genes through a unique pathway

PMID: 18054516, 15101709, 16769767, 12513906 type I IFNs promote the differentiation of human blood monocytes into DC and contribute to their maturation

PMID: 18054516, 15101709, 16769767, 12513906 type I IFNs promote the differentiation of human blood monocytes into DC and contribute to their maturation

indirect

PMID: 18054516, 15101709, 16769767, 12513906 In particular, it was reported that blood monocytes maintained in culture for 3 days with IFN-α express high levels of HLA-DR, of costimulatory molecules CD80, CD86 and of adhesion molecule CD54

indirect

PMID: 18054516, 15101709, 16769767, 12513906 In particular, it was reported that blood monocytes maintained in culture for 3 days with IFN-α express high levels of HLA-DR, of costimulatory molecules CD80, CD86 and of adhesion molecule CD54

indirect

PMID: 18054516, 15101709, 16769767, 12513906 In particular, it was reported that blood monocytes maintained in culture for 3 days with IFN-α express high levels of HLA-DR, of costimulatory molecules CD80, CD86 and of adhesion molecule CD54

indirect

PMID: 18054516, 15101709, 16769767, 12513906 In particular, it was reported that blood monocytes maintained in culture for 3 days with IFN-α express high levels of HLA-DR, of costimulatory molecules CD80, CD86 and of adhesion molecule CD54

indirect

PMID: 18054516, 15101709, 16769767, 12513906 In particular, it was reported that blood monocytes maintained in culture for 3 days with IFN-α express high levels of HLA-DR, of costimulatory molecules CD80, CD86 and of adhesion molecule CD54

indirect

PMID: 18054516, 15101709, 16769767, 12513906 In particular, it was reported that blood monocytes maintained in culture for 3 days with IFN-α express high levels of HLA-DR, of costimulatory molecules CD80, CD86 and of adhesion molecule CD54

indirect

PMID: 18054516, 15101709, 16769767, 12513906 In particular, it was reported that blood monocytes maintained in culture for 3 days with IFN-α express high levels of HLA-DR, of costimulatory molecules CD80, CD86 and of adhesion molecule CD54

indirect

PMID: 18054516, 15101709, 16769767, 12513906 In particular, it was reported that blood monocytes maintained in culture for 3 days with IFN-α express high levels of HLA-DR, of costimulatory molecules CD80, CD86 and of adhesion molecule CD54

indirect

PMID: 18054516 In particular, the expression of CXCR3 binding chemokines, CXCL9, CXCL10 and CXCL11, is dependent on type I IFNs.

indirect

PMID: 18054516 In particular, the expression of CXCR3 binding chemokines, CXCL9, CXCL10 and CXCL11, is dependent on type I IFNs.

indirect

PMID: 18054516 In particular, the expression of CXCR3 binding chemokines, CXCL9, CXCL10 and CXCL11, is dependent on type I IFNs.

indirect

PMID: 18054516 In particular, the expression of CXCR3 binding chemokines, CXCL9, CXCL10 and CXCL11, is dependent on type I IFNs.

indirect

PMID: 18054516 In particular, the expression of CXCR3 binding chemokines, CXCL9, CXCL10 and CXCL11, is dependent on type I IFNs.

indirect

PMID: 18054516 In particular, the expression of CXCR3 binding chemokines, CXCL9, CXCL10 and CXCL11, is dependent on type I IFNs.

indirect

PMID: 18054516 In particular, the expression of CXCR3 binding chemokines, CXCL9, CXCL10 and CXCL11, is dependent on type I IFNs.

indirect

PMID: 18054516 In particular, the expression of CXCR3 binding chemokines, CXCL9, CXCL10 and CXCL11, is dependent on type I IFNs.

indirect

PMID: 18054516 In particular, the expression of CXCR3 binding chemokines, CXCL9, CXCL10 and CXCL11, is dependent on type I IFNs.

indirect

PMID: 18054516 In particular, the expression of CXCR3 binding chemokines, CXCL9, CXCL10 and CXCL11, is dependent on type I IFNs.

indirect

PMID: 18054516 In particular, the expression of CXCR3 binding chemokines, CXCL9, CXCL10 and CXCL11, is dependent on type I IFNs.

indirect

PMID: 18054516 In particular, the expression of CXCR3 binding chemokines, CXCL9, CXCL10 and CXCL11, is dependent on type I IFNs.

indirect

PMID: 18054516, 10604988 On the other hand, CD40-dependent IL-12 production from monocyte-derived DC was shown to be impaired by IFN-β

indirect

PMID: 18054516, 10604988 On the other hand, CD40-dependent IL-12 production from monocyte-derived DC was shown to be impaired by IFN-β

indirect

PMID: 18054516, 16624932 Among the STAT transcription factors involved in type I IFN signalling, STAT-1 and -2 contents are increased in DC stimulated with LPS or poly I:C

indirect

PMID: 18054516, 16624932 Among the STAT transcription factors involved in type I IFN signalling, STAT-1 and -2 contents are increased in DC stimulated with LPS or poly I:C

indirect

PMID: 18054516, 16624932 Among the STAT transcription factors involved in type I IFN signalling, STAT-1 and -2 contents are increased in DC stimulated with LPS or poly I:C

indirect

PMID: 18054516, 16624932 Among the STAT transcription factors involved in type I IFN signalling, STAT-1 and -2 contents are increased in DC stimulated with LPS or poly I:C

PMID: 18054516 Thus, under inflammatory conditions, NF-κB is activated and, in turn, induces STAT-4 whose activation by type I IFNs may regulate the transcription of specific target genes in mature DC.

PMID: 18054516 Thus, under inflammatory conditions, NF-κB is activated and, in turn, induces STAT-4 whose activation by type I IFNs may regulate the transcription of specific target genes in mature DC.

indirect

PMID: 18054516 Thus, under inflammatory conditions, NF-κB is activated and, in turn, induces STAT-4 whose activation by type I IFNs may regulate the transcription of specific target genes in mature DC.

PMID: 18054516 Thus, under inflammatory conditions, NF-κB is activated and, in turn, induces STAT-4 whose activation by type I IFNs may regulate the transcription of specific target genes in mature DC.

indirect

PMID: 18054516 STAT-4 expression can be induced in human primary DC by multiple stimuli activating NF-κB transcription factors, such as the ligands for TLR4, TLR2 and TLR3, various pathogens, CD40L and the pro-inflammatory cytokines TNF-α and IL-1β. PMID: 18054516 Thus, under inflammatory conditions, NF-κB is activated and, in turn, induces STAT-4 whose activation by type I IFNs may regulate the transcription of specific target genes in mature DC.

indirect

PMID: 18054516 STAT-4 expression can be induced in human primary DC by multiple stimuli activating NF-κB transcription factors, such as the ligands for TLR4, TLR2 and TLR3, various pathogens, CD40L and the pro-inflammatory cytokines TNF-α and IL-1β. PMID: 18054516 Thus, under inflammatory conditions, NF-κB is activated and, in turn, induces STAT-4 whose activation by type I IFNs may regulate the transcription of specific target genes in mature DC.

indirect

PMID: 18054516 STAT-4 expression can be induced in human primary DC by multiple stimuli activating NF-κB transcription factors, such as the ligands for TLR4, TLR2 and TLR3, various pathogens, CD40L and the pro-inflammatory cytokines TNF-α and IL-1β. PMID: 18054516 Thus, under inflammatory conditions, NF-κB is activated and, in turn, induces STAT-4 whose activation by type I IFNs may regulate the transcription of specific target genes in mature DC.

indirect

PMID: 18054516 STAT-4 expression can be induced in human primary DC by multiple stimuli activating NF-κB transcription factors, such as the ligands for TLR4, TLR2 and TLR3, various pathogens, CD40L and the pro-inflammatory cytokines TNF-α and IL-1β. PMID: 18054516 Thus, under inflammatory conditions, NF-κB is activated and, in turn, induces STAT-4 whose activation by type I IFNs may regulate the transcription of specific target genes in mature DC.

indirect

PMID: 18054516 STAT-4 expression can be induced in human primary DC by multiple stimuli activating NF-κB transcription factors, such as the ligands for TLR4, TLR2 and TLR3, various pathogens, CD40L and the pro-inflammatory cytokines TNF-α and IL-1β. PMID: 18054516 Thus, under inflammatory conditions, NF-κB is activated and, in turn, induces STAT-4 whose activation by type I IFNs may regulate the transcription of specific target genes in mature DC.

indirect

PMID: 18054516 STAT-4 expression can be induced in human primary DC by multiple stimuli activating NF-κB transcription factors, such as the ligands for TLR4, TLR2 and TLR3, various pathogens, CD40L and the pro-inflammatory cytokines TNF-α and IL-1β. PMID: 18054516 Thus, under inflammatory conditions, NF-κB is activated and, in turn, induces STAT-4 whose activation by type I IFNs may regulate the transcription of specific target genes in mature DC.