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PMID: 16446382
These include TLR3, TLR7/8, and TLR9, which sense double-stranded (ds)RNA, single-stranded (ss)RNA, and ssDNA, respectively.

PMID: 16446382
A likely interpretation of these results is that high concentrations of endosomal ssPD-DNA, or other nonstimulatory oligonucleotides, can activate TLR9 in a CpG-independent fashion.</csml:comment>
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PMID: 16446382
These include TLR3, TLR7/8, and TLR9, which sense double-stranded (ds)RNA, single-stranded (ss)RNA, and ssDNA, respectively.</csml:comment>
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PMID: 16446382
These include TLR3, TLR7/8, and TLR9, which sense double-stranded (ds)RNA, single-stranded (ss)RNA, and ssDNA, respectively.</csml:comment>
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PMID: 16446382
Two major signaling pathways are activated upon ligand-driven TLR dimerization.</csml:comment>
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PMID: 16446382, 11861602, 15229469, 15207506
Other TLRs, in contrast, reside on the cell membrane. These include TLR2, TLR4, TLR5, and TLR11, which recognize lipopeptides, lipopolysaccharide, flagellin, and propellin, respectively.</csml:comment>
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PMID: 16446382
These include TLR3, TLR7/8, and TLR9, which sense double-stranded (ds)RNA, single-stranded (ss)RNA, and ssDNA, respectively.</csml:comment>
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PMID: 16446382, 11861602, 15229469, 15207506
Other TLRs, in contrast, reside on the cell membrane. These include TLR2, TLR4, TLR5, and TLR11, which recognize lipopeptides, lipopolysaccharide, flagellin, and propellin, respectively.</csml:comment>
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<csml:comment type="text">

PMID: 16446382
Two major signaling pathways are activated upon ligand-driven TLR dimerization.</csml:comment>
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PMID: 16446382
One pathway requires the adaptor molecule MyD88 and culminates in the production of type I interferons (IFNs) or NF-kappaB&#8211;dependent proinflammatory cytokines including TNF and interleukin (IL)-12.</csml:comment>
</csml:comments>
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</csml:processKinetic>
</csml:processSimulationProperty>
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<csml:comment type="text">

PMID: 16446382
The other pathway requires the adaptor molecule TRIF and primarily culminates in the production of type I IFNs.</csml:comment>
</csml:comments>
</csml:process>
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Indirect</csml:comment>
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</csml:connector>
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PMID: 16446382
One pathway requires the adaptor molecule MyD88 and culminates in the production of type I interferons (IFNs) or NF-kappaB&#8211;dependent proinflammatory cytokines including TNF and interleukin (IL)-12.</csml:comment>
</csml:comments>
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Indirect</csml:comment>
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Indirect</csml:comment>
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<csml:comment type="text">

PMID: 16446382
One pathway requires the adaptor molecule MyD88 and culminates in the production of type I interferons (IFNs) or NF-kappaB&#8211;dependent proinflammatory cytokines including TNF and interleukin (IL)-12.</csml:comment>
</csml:comments>
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Indirect</csml:comment>
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Indirect</csml:comment>
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PMID: 16446382
One pathway requires the adaptor molecule MyD88 and culminates in the production of type I interferons (IFNs) or NF-kappaB&#8211;dependent proinflammatory cytokines including TNF and interleukin (IL)-12.</csml:comment>
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PMID: 16446382
One pathway requires the adaptor molecule MyD88 and culminates in the production of type I interferons (IFNs) or NF-kappaB&#8211;dependent proinflammatory cytokines including TNF and interleukin (IL)-12.</csml:comment>
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PMID: 16446382
One pathway requires the adaptor molecule MyD88 and culminates in the production of type I interferons (IFNs) or NF-kappaB&#8211;dependent proinflammatory cytokines including TNF and interleukin (IL)-12.</csml:comment>
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PMID: 16446382
One pathway requires the adaptor molecule MyD88 and culminates in the production of type I interferons (IFNs) or NF-kappaB&#8211;dependent proinflammatory cytokines including TNF and interleukin (IL)-12.

PMID: 16446382
After ligation of TLR7, TLR8, and TLR9, the adaptor molecule MyD88 is recruited and drives the production of proinflammatory cytokine genes or type 1 interferon genes.</csml:comment>
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PMID: 16446382
One pathway requires the adaptor molecule MyD88 and culminates in the production of type I interferons (IFNs) or NF-kappaB&#8211;dependent proinflammatory cytokines including TNF and interleukin (IL)-12.

PMID: 16446382
After ligation of TLR7, TLR8, and TLR9, the adaptor molecule MyD88 is recruited and drives the production of proinflammatory cytokine genes or type 1 interferon genes.</csml:comment>
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<csml:comment type="text">

PMID: 16446382
The other pathway requires the adaptor molecule TRIF and primarily culminates in the production of type I IFNs.</csml:comment>
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PMID: 16446382, 11861602, 15229469, 15207506
Other TLRs, in contrast, reside on the cell membrane. These include TLR2, TLR4, TLR5, and TLR11, which recognize lipopeptides, lipopolysaccharide, flagellin, and propellin, respectively.</csml:comment>
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PMID: 16446382, 11861602, 15229469, 15207506
Other TLRs, in contrast, reside on the cell membrane. These include TLR2, TLR4, TLR5, and TLR11, which recognize lipopeptides, lipopolysaccharide, flagellin, and propellin, respectively.</csml:comment>
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Indirect</csml:comment>
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PMID: 16446382
TLR3 ligation triggers type 1 interferon genes via the adaptor protein TRIF.</csml:comment>
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<csml:comments>
<csml:comment type="text">

PMID: 16446382
TLR3 ligation triggers type 1 interferon genes via the adaptor protein TRIF.</csml:comment>
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PMID: 16446382, 11948342
In this system, the RF+ BCR first recognizes the isotype of the autoantibody, and this recognition triggers the subsequent translocation of the ICs into TLR-expressing endosomes.</csml:comment>
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PMID: 16446382, 11948342
In this system, the RF+ BCR first recognizes the isotype of the autoantibody, and this recognition triggers the subsequent translocation of the ICs into TLR-expressing endosomes.

PMID: 16446382, 15197227, 15668740
Similarly, anti-DNA ICs that are translocated to endosomes via FcgammaRIII-mediated (mouse) or FcgammaRIIa-mediated (human) endocytosis activate the TLR9-dependent production of cytokines, including type I IFNs.</csml:comment>
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PMID: 16446382, 15197227, 15668740
Similarly, anti-DNA ICs that are translocated to endosomes via FcgammaRIII-mediated (mouse) or FcgammaRIIa-mediated (human) endocytosis activate the TLR9-dependent production of cytokines, including type I IFNs.

PMID: 16446382
Thus, in SLE, both self-RNA and self-DNA can act as ligands for TLR7 and TLR9, respectively, provided they do not contain certain posttranscriptional nucleoside modifications.</csml:comment>
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PMID: 16446382, 11948342
In this system, the RF+ BCR first recognizes the isotype of the autoantibody, and this recognition triggers the subsequent translocation of the ICs into TLR-expressing endosomes

PMID: 16446382, 15197227, 15668740
Similarly, anti-DNA ICs that are translocated to endosomes via FcgammaRIII-mediated (mouse) or FcgammaRIIa-mediated (human) endocytosis activate the TLR9-dependent production of cytokines, including type I IFNs.</csml:comment>
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PMID: 16446382, 15197227, 15668740
Similarly, anti-DNA ICs that are translocated to endosomes via FcgammaRIII-mediated (mouse) or FcgammaRIIa-mediated (human) endocytosis activate the TLR9-dependent production of cytokines, including type I IFNs.</csml:comment>
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PMID: 16446382, 15197227, 15668740
Similarly, anti-DNA ICs that are translocated to endosomes via FcgammaRIII-mediated (mouse) or FcgammaRIIa-mediated (human) endocytosis activate the TLR9-dependent production of cytokines, including type I IFNs.</csml:comment>
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PMID: 16446382, 16368889, 16230478, 16260486
ICs containing U1 small nuclear ribonucleotide proteins, which are found in a subset of SLE patients, activate the TLR7-dependent production of type I IFNs and other proinflammatory cytokines by murine pDCs.

PMID: 16446382
Thus, in SLE, both self-RNA and self-DNA can act as ligands for TLR7 and TLR9, respectively, provided they do not contain certain posttranscriptional nucleoside modifications.</csml:comment>
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PMID: 16446382, 16368889, 16230478, 16260486
ICs containing U1 small nuclear ribonucleotide proteins, which are found in a subset of SLE patients, activate the TLR7-dependent production of type I IFNs and other proinflammatory cytokines by murine pDCs.</csml:comment>
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PMID: 16446382, 16368889, 16230478, 16260486
ICs containing U1 small nuclear ribonucleotide proteins, which are found in a subset of SLE patients, activate the TLR7-dependent production of type I IFNs and other proinflammatory cytokines by murine pDCs.</csml:comment>
</csml:comments>
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PMID: 16446382
In this system, the RNA is recognized by the cytoplasmic helicase domain of the helicase protein retinoic acid&#8211;induced gene 1 (RIG-1).</csml:comment>
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PMID: 16446382, 15208624, 16177806
The downstream signaling events that result from this recognition require the NH2-terminal caspase recruitment domain (CARD) of RIG-1, which binds to the adaptor molecule Cardif (also called IPS-1.</csml:comment>
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PMID: 16446382
After ligation of TLR7, TLR8, and TLR9, the adaptor molecule MyD88 is recruited and drives the production of proinflammatory cytokine genes or type 1 interferon genes.</csml:comment>
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PMID: 16446382
After ligation of TLR7, TLR8, and TLR9, the adaptor molecule MyD88 is recruited and drives the production of proinflammatory cytokine genes or type 1 interferon genes.</csml:comment>
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PMID: 16446382
After ligation of TLR7, TLR8, and TLR9, the adaptor molecule MyD88 is recruited and drives the production of proinflammatory cytokine genes or type 1 interferon genes.</csml:comment>
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PMID: 16446382
After ligation of TLR7, TLR8, and TLR9, the adaptor molecule MyD88 is recruited and drives the production of proinflammatory cytokine genes or type 1 interferon genes.</csml:comment>
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PMID: 16446382
After ligation of TLR7, TLR8, and TLR9, the adaptor molecule MyD88 is recruited and drives the production of proinflammatory cytokine genes or type 1 interferon genes.</csml:comment>
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PMID: 16446382
After ligation of TLR7, TLR8, and TLR9, the adaptor molecule MyD88 is recruited and drives the production of proinflammatory cytokine genes or type 1 interferon genes.</csml:comment>
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PMID: 16446382
Cardiff /IPS-1 in turn interacts with Ikkalpha/beta/gamma kinases and thus activates IRF3.</csml:comment>
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Indirect</csml:comment>
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PMID: 16446282
Although viral dsRNA is known to be sensed by TLR3, DCs or fibroblasts that lack TLR3 still produce type I IFNs after intracellular introduction of dsRNA molecules.</csml:comment>
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PMID: 16446382, 15210742
This TLR3-independent induction does not require TRIF, but depends on the kinase TBK1 (TANK-binding kinase-1) and the transcription factor IRF-3 (IFN regulatory factor-3).

PMID: 16446382
Cardiff /IPS-1 in turn interacts with Ikkalpha/beta/gamma kinases and thus activates IRF3.</csml:comment>
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PMID: 16446382
Another candidate for the sensing of cytoplasmic dsRNA molecules is Mda5 (melanoma differentiation-associated gene 5, also termed Helicard).</csml:comment>
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