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xlink:show="other" xlink:type="simple" r="50%" cx="50%" fx="50%" cy="50%" fy="50%" xlink:actuate="onLoad"> <stop style="stop-color:white;stop-opacity:1;" offset="0%"/> <stop style="stop-color:#cccc00;stop-opacity:1;" offset="0%"/> </radialGradient> </defs> <path d="M 59.9996 48.5409 c 3.1032 -10.5054 13.6618 -3.3909 -13.3958 -8.9618 l 13.3958 -28.1201 c -9.5468 -6.053 0.8309 -13.4051 -13.1014 9.3474 l -23.9804 -20.8065 c -9.0031 6.7646 -13.1481 -4.8939 5.2987 14.739 l -28.2165 15.261 c 3.9824 10.2338 -8.9568 10.3804 16.3763 -0.2382 l 6.5415 30.2382 c 11.4643 -0.4396 7.6125 11.3094 4.8225 -14.886 l 32.2597 3.4273 z" style="fill:url(#MO_f4eb03);stroke:none;"/> </svg> PMID:18262306 A mouse forward genetics screening identified Unc93B as a molecule essential for TLR3, TLR7 and TLR9 signaling. This protein is known to interact with a membrane spanning domain of TLR9.

PMID: 18262306,10549626,9851930,10201887 TLR2 (together with TLR1 or TLR6) and TLR4 are the receptors mainly involved in the recognition of bacteria-derived ligands, such as microbial lipoproteins and LPS, respectively

PMID: 18262306,10549626,9851930,10201887 TLR2 (together with TLR1 or TLR6) and TLR4 are the receptors mainly involved in the recognition of bacteria-derived ligands, such as microbial lipoproteins and LPS, respectively

PMID: 18262306,10549626,9851930,10201887 TLR2 (together with TLR1 or TLR6) and TLR4 are the receptors mainly involved in the recognition of bacteria-derived ligands, such as microbial lipoproteins and LPS, respectively

PMID: 18262306,11607032,14976261,14976262,11812998 TLR3 and 7 (and possibly 8) are involved in the recognition of double-stranded (ds) and single-stranded (ss) RNA, respectively

PMID: 18262306,11607032,14976261,14976262,11812998 TLR3 and 7 (and possibly 8) are involved in the recognition of double-stranded (ds) and single-stranded (ss) RNA, respectively

PMID: 18262306,11607032,14976261,14976262,11812998 TLR3 and 7 (and possibly 8) are involved in the recognition of double-stranded (ds) and single-stranded (ss) RNA, respectively

PMID: 18262306,11130078 TLR9 was first cloned and identified as a receptor for unmethylated CpG-DNA as well as for bacterial DNA in 2000

PMID: 18262306,11130078 TLR9 was first cloned and identified as a receptor for unmethylated CpG-DNA as well as for bacterial DNA in 2000 PMID: 18262306 TLR9 also recognizes bacterial and viral DNA

PMID: 18262306,15630134 In addition to DNA, hemozoin (HZ) derived from the malaria parasite Plasmodium acts as a TLR9 ligand

PMID: 18262306 MyD88, one of these adaptors containing a TIR domain and a death domain (DD), is known to be essential for initiating TLR9 signaling.

PMID: 18262306 MyD88 in turn interacts with interleukin-1 receptor-associated kinase-1 (IRAK-1) and IRAK-4 through its DD.

PMID: 18262306,17485511 IRAK-4 and its kinase activity are shown to be essential for TLR9-mediated cytokine production PMID: 18262306 IRAK-1 is a known substrate of IRAK-4, and phosphorylated IRAK-1 upregulates its kinase activity, and subsequently recruits tumor necrosis factor associated factor 6 (TRAF6).

PMID: 18262306 IRAK-1 is a known substrate of IRAK-4, and phosphorylated IRAK-1 upregulates its kinase activity, and subsequently recruits tumor necrosis factor associated factor 6 (TRAF6).

indirect

PMID: 18262306,11460167 Downstream of TRAF6, transforming growth factor-beta associated kinase 1 (TAK1) is activated to the phosphorylate IKappaB kinase (IKK) complex, which phosphorylates IKappaB to induce nuclear translocation of NF-KappaB

indirect

PMID: 18262306, 11460167 Downstream of TRAF6, transforming growth factor-beta associated kinase 1 (TAK1) is activated to the phosphorylate IKappaB kinase (IKK) complex, which phosphorylates IKappaB to induce nuclear translocation of NF-KappaB

indirect

PMID: 18262306, 11460167 Downstream of TRAF6, transforming growth factor-beta associated kinase 1 (TAK1) is activated to the phosphorylate IKappaB kinase (IKK) complex, which phosphorylates IKappaB to induce nuclear translocation of NF-KappaB

PMID: 18262306, 11460167 Downstream of TRAF6, transforming growth factor-beta associated kinase 1 (TAK1) is activated to the phosphorylate IKappaB kinase (IKK) complex, which phosphorylates IκB to induce nuclear translocation of NF-KappaB

indirect

indirect

PMID: 18262306 Figure1 PMID: 18262306,16862162,16186825 A study of Ubc13-deificient mice revealed that UBC13 is prerequisite for the activation of mitogen-activated protein (MAP) kinases, but is dispensable for NF-KappaB activation, whereas TAK1 is required for both

PMID: 18262306 Figure1

indirect

PMID: 18262306 Figure 1

PMID: 18262306 Figure 1

indirect

PMID: 18262306 Transcription factors NF-KappaB and AP-1 are responsible for the transcription of proinflammatory cytokine genes, including TNF-alpha, IL-6 and IL-12. PMID: 18262306,12626561 Upon B or K-type CpG-DNA stimulation, cDCs and macrophages produce proinflammatory cytokines, such as TNF-alpha, IL-6 and IL-12, and upregulate surface expression of MHC class II and co-stimulatory molecules

indirect

PMID: 18262306 Transcription factors NF-KappaB and AP-1 are responsible for the transcription of proinflammatory cytokine genes, including TNF-alpha, IL-6 and IL-12. PMID: 18262306,12626561 Upon B or K-type CpG-DNA stimulation, cDCs and macrophages produce proinflammatory cytokines, such as TNF-alpha, IL-6 and IL-12, and upregulate surface expression of MHC class II and co-stimulatory molecules

indirect

PMID: 18262306 Transcription factors NF-KappaB and AP-1 are responsible for the transcription of proinflammatory cytokine genes, including TNF-alpha, IL-6 and IL-12. PMID: 18262306,12626561 Upon B or K-type CpG-DNA stimulation, cDCs and macrophages produce proinflammatory cytokines, such as TNF-alpha, IL-6 and IL-12, and upregulate surface expression of MHC class II and co-stimulatory molecules

indirect

PMID: 18262306 Transcription factors NF-KappaB and AP-1 are responsible for the transcription of proinflammatory cytokine genes, including TNF-alpha, IL-6 and IL-12. PMID: 18262306,12626561 Upon B or K-type CpG-DNA stimulation, cDCs and macrophages produce proinflammatory cytokines, such as TNF-alpha, IL-6 and IL-12, and upregulate surface expression of MHC class II and co-stimulatory molecules

indirect

PMID: 18262306 Transcription factors NF-KappaB and AP-1 are responsible for the transcription of proinflammatory cytokine genes, including TNF-alpha, IL-6 and IL-12. PMID: 18262306,12626561 Upon B or K-type CpG-DNA stimulation, cDCs and macrophages produce proinflammatory cytokines, such as TNF-alpha, IL-6 and IL-12, and upregulate surface expression of MHC class II and co-stimulatory molecules

indirect

PMID: 18262306 Transcription factors NF-KappaB and AP-1 are responsible for the transcription of proinflammatory cytokine genes, including TNF-alpha, IL-6 and IL-12. PMID: 18262306,12626561 Upon B or K-type CpG-DNA stimulation, cDCs and macrophages produce proinflammatory cytokines, such as TNF-alpha, IL-6 and IL-12, and upregulate surface expression of MHC class II and co-stimulatory molecules

PMID: 18262306 IRF-5 interacts with MyD88 and TLR stimulation induces nuclear translocation of IRF-5 which regulates the production of several cytokines such as IL-6, IL-12, and TNF-alpha

PMID: 18262306 IRF-5 interacts with MyD88 and TLR stimulation induces nuclear translocation of IRF-5 which regulates the production of several cytokines such as IL-6, IL-12, and TNF-alpha

indirect

PMID: 18262306 IRF-5 interacts with MyD88 and TLR stimulation induces nuclear translocation of IRF-5 which regulates the production of several cytokines such as IL-6, IL-12, and TNF-alpha

indirect

PMID: 18262306 IRF-5 interacts with MyD88 and TLR stimulation induces nuclear translocation of IRF-5 which regulates the production of several cytokines such as IL-6, IL-12, and TNF-alpha

indirect

PMID: 18262306 IRF-5 interacts with MyD88 and TLR stimulation induces nuclear translocation of IRF-5 which regulates the production of several cytokines such as IL-6, IL-12, and TNF-alpha

indirect

PMID: 18262306 IRF-5 interacts with MyD88 and TLR stimulation induces nuclear translocation of IRF-5 which regulates the production of several cytokines such as IL-6, IL-12, and TNF-alpha

indirect

PMID: 18262306 IRF-5 interacts with MyD88 and TLR stimulation induces nuclear translocation of IRF-5 which regulates the production of several cytokines such as IL-6, IL-12, and TNF-alpha

indirect

PMID: 18262306 IRF-5 interacts with MyD88 and TLR stimulation induces nuclear translocation of IRF-5 which regulates the production of several cytokines such as IL-6, IL-12, and TNF-alpha

indirect

PMID: 18262306,14716310 TLR9 is originally localized in the ER, and then migrates to the endosome when the cells are stimulated

indirect

PMID: 18262306,12626561 Upon B or K-type CpG-DNA stimulation, cDCs and macrophages produce proinflammatory cytokines, such as TNF-alpha, IL-6 and IL-12, and upregulate surface expression of MHC class II and co-stimulatory molecules

indirect

indirect

PMID: 18262306,12626561 Upon B or K-type CpG-DNA stimulation, cDCs and macrophages produce proinflammatory cytokines, such as TNF-alpha, IL-6 and IL-12, and upregulate surface expression of MHC class II and co-stimulatory molecules

indirect

indirect

PMID: 18262306 cDC produces IL-15 upon TLR9 stimulation

indirect

PMID: 18262306 IL-15 in turn activates pDC to express CD40L on its surface.

indirect

indirect

PMID: 18262306 At the same time, TLR9 signaling facilitates expression of CD40 on cDC

PMID: 18262306 Consequently, crosstalk between cDC and pDC via CD40-CD40L ligation leads to production of IL-12 from cDC.

indirect

indirect

PMID: 18262306 Consequently, crosstalk between cDC and pDC via CD40-CD40L ligation leads to production of IL-12 from cDC.

PMID: 18262306,17018642 It was revealed that IRF-1 also interacts with MyD88, and IRF-1, but not IRF-7, and is activated in response to TLR9 stimulation of cDCs to control the expression of IFN-beta

PMID: 18262306,17018642 It was revealed that IRF-1 also interacts with MyD88, and IRF-1, but not IRF-7, and is activated in response to TLR9 stimulation of cDCs to control the expression of IFN-beta

indirect

PMID: 18262306,17018642 It was revealed that IRF-1 also interacts with MyD88, and IRF-1, but not IRF-7, and is activated in response to TLR9 stimulation of cDCs to control the expression of IFN-beta

PMID: 18262306,11130078 TLR9 was first cloned and identified as a receptor for unmethylated CpG-DNA as well as for bacterial DNA in 2000

PMID: 18262306 MyD88, one of these adaptors containing a TIR domain and a death domain (DD), is known to be essential for initiating TLR9 signaling.

PMID: 18262306,15361868 IRF-7 directly interacts with MyD88 and forms a large complex with IRAK-1, IRAK-4 and TRAF6 in pDCs

PMID: 18262306 IRF-7 is phosphorylated in the complex and translocates into the nucleus to induce transcription of type I IFNs and IFN-inducible genes.

PMID: 18262306 IRF-7 is phosphorylated in the complex and translocates into the nucleus to induce transcription of type I IFNs and IFN-inducible genes.

inidrect

PMID: 18262306 IRF-7 is phosphorylated in the complex and translocates into the nucleus to induce transcription of type I IFNs and IFN-inducible genes.

indirect

PMID: 18262306 IRF-7 is phosphorylated in the complex and translocates into the nucleus to induce transcription of type I IFNs and IFN-inducible genes.

PMID: 18262306 MyD88 in turn interacts with interleukin-1 receptor-associated kinase-1 (IRAK-1) and IRAK-4 through its DD.

PMID: 18262306,17485511 IRAK-4 and its kinase activity are shown to be essential for TLR9-mediated cytokine production PMID: 18262306 IRAK-1 is a known substrate of IRAK-4, and phosphorylated IRAK-1 upregulates its kinase activity, and subsequently recruits tumor necrosis factor associated factor 6 (TRAF6).

PMID: 18262306 IRAK-1 is a known substrate of IRAK-4, and phosphorylated IRAK-1 upregulates its kinase activity, and subsequently recruits tumor necrosis factor associated factor 6 (TRAF6).

PMID: 18262306 TLR9 also recognizes bacterial and viral DNA

PMID: 18262306,16424890 Nevertheless, recent studies revealed that cytosolic PRRs called Retinoic acid-inducible gene (RIG-I)-like helicases (RLHs) can recognize viral RNA in the cytosol

PMID: 18262306,16424890 Nevertheless, recent studies revealed that cytosolic PRRs called Retinoic acid-inducible gene (RIG-I)-like helicases (RLHs) can recognize viral RNA in the cytosol PMID: 18262306 The recognition of viral RNAs by these helicases induces production of type I IFNs and an associated antiviral response.

indirect

PMID: 18262306 The recognition of viral RNAs by these helicases induces production of type I IFNs and an associated antiviral response.

indirect

PMID: 18262306 The recognition of viral RNAs by these helicases induces production of type I IFNs and an associated antiviral response.

PMID: 18262306,17618271 Recently, a potential cytoplasmic DNA receptor named DAI (also known as DLM1 or ZBP1) was identified