PMID: 17544561,12900525,15272082,15345224,12470615,15113904,14976261,16224540,15034168 TLR9 is the receptor for both CpG sequences and double-stranded DNA from herpes simplex virus and cytomegalovirus, while the ligands for TLR7 include the imadazoquinolones and single stranded RNA such as found in viruses like HIV-1

PMID: 17544561,16286015,15361868,15492225 This association, which requires that the TLR and ligand remain for an extended time in the endosome as opposed to being transferred to the lysosome for induction of IFN, also requires IRAK-4 and the ubiquitin ligase action of TRAF6 for the activation of IRF-7

PMID: 17544561, 15815647 MyD88, which is required for signaling through TLR7 and TLR9, forms a complex with IRF-7 that is required for the signaling for type I IFN production in the pDC

PMID: 17544561, 15815647 MyD88, which is required for signaling through TLR7 and TLR9, forms a complex with IRF-7 that is required for the signaling for type I IFN production in the pDC

PMID: 17544561, 15767370 A recent study demonstrated that the kinase that interacts with and phosphorylates the IRF-7 is IRAK-1; IRAK-1 deficient mice were found to be severely compromised in their ability to activate IRF-7 and induce type 1 IFN

PMID: 17544561, 15767370 A recent study demonstrated that the kinase that interacts with and phosphorylates the IRF-7 is IRAK-1; IRAK-1 deficient mice were found to be severely compromised in their ability to activate IRF-7 and induce type 1 IFN

PMID: 17544561, 15767370 A recent study demonstrated that the kinase that interacts with and phosphorylates the IRF-7 is IRAK-1; IRAK-1 deficient mice were found to be severely compromised in their ability to activate IRF-7 and induce type 1 IFN PMID: 17544561, 15815647 MyD88, which is required for signaling through TLR7 and TLR9, forms a complex with IRF-7 that is required for the signaling for type I IFN production in the pDC PMID: 17544561 These IFNs are translated, then secreted, and signal through the IFN-alpha/beta receptor and, through ISGF3 (comprised of STAT1, STAT2 and IRF-9), upregulate IRF-7 expression which is needed for the expression of the full range and magnitude of the IFN-alpha genes. PMID: 17544561 They further reported that cross-linking of this receptor on the pDC inhibits CpG and Flu-induced type I IFN and cytokine expression by these cells.

PMID: 17544561 cDC have an additional mechanism for the induction of type I IFN in response to dsRNA viruses that goes via the dsRNA sensor, TLR3 in the endosomes.

PMID: 17544561,15711573 TLR3 signaling utilizes the adaptor molecule TRIF rather than the IPS-1/MAV5 used in the RIG-I/MDA-5 pathway

PMID: 17544561,16210631,15208624 dsRNA is well-known for its ability to activate PKR, but, more recently, the role for the retinoic acid-inducible gene-I (RIG-I) encoded helicases and melanoma differentiation-associated gene 5 (MDA-5) have been strongly implicated as the prevalent cytoplasmic receptors for dsRNA leading to IFN-alpha production

PMID: 17544561,16210631,15208624 dsRNA is well-known for its ability to activate PKR, but, more recently, the role for the retinoic acid-inducible gene-I (RIG-I) encoded helicases and melanoma differentiation-associated gene 5 (MDA-5) have been strongly implicated as the prevalent cytoplasmic receptors for dsRNA leading to IFN-alpha production

PMID: 17544561,12900525,15272082,15345224,12470615,15113904,14976261,16224540,15034168 TLR9 is the receptor for both CpG sequences and double-stranded DNA from herpes simplex virus and cytomegalovirus, while the ligands for TLR7 include the imadazoquinolones and single stranded RNA such as found in viruses like HIV-1

PMID: 17544561 Figure 1 PMID: 17544561, 15711573 TLR3 signaling utilizes the adaptor molecule TRIF rather than the IPS-1/MAV5 used in the RIG-I/MDA-5 pathway

PMID: 17544561 Figure 1 PMID: 17544561, 15711573 TLR3 signaling utilizes the adaptor molecule TRIF rather than the IPS-1/MAV5 used in the RIG-I/MDA-5 pathway

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PMID: 17544561 Figure 1

PMID: 17544561 Figure 1

PMID: 17544561 Figure 1

PMID: 17544561 Figure 1

PMID: 17544561 Figure 1 PMID: 17544561, 16210631, 15208624 dsRNA is well-known for its ability to activate PKR, but, more recently, the role for the retinoic acid-inducible gene-I (RIG-I) encoded helicases and melanoma differentiation-associated gene 5 (MDA-5) have been strongly implicated as the prevalent cytoplasmic receptors for dsRNA leading to IFN-alpha production PMID: 17544561 cDC have an additional mechanism for the induction of type I IFN in response to dsRNA viruses that goes via the dsRNA sensor, TLR3 in the endosomes

PMID: 17544561,15265881 our group demonstrated that human peripheral blood pDC express basal levels of TLR4 and respond to LPS stimulation with upregulation of TLR4 message and protein as well as up-regulate the expression of the transcription factor, IRF-7

PMID: 17544561,15265881 our group demonstrated that human peripheral blood pDC express basal levels of TLR4 and respond to LPS stimulation with upregulation of TLR4 message and protein as well as up-regulate the expression of the transcription factor, IRF-7

PMID: 17544561,12900525,15272082,15345224,12470615,15113904,14976261,16224540,15034168 TLR9 is the receptor for both CpG sequences and double-stranded DNA from herpes simplex virus and cytomegalovirus, while the ligands for TLR7 include the imadazoquinolones and single stranded RNA such as found in viruses like HIV-1

PMID: 17544561,15265881 our group demonstrated that human peripheral blood pDC express basal levels of TLR4 and respond to LPS stimulation with upregulation of TLR4 message and protein as well as up-regulate the expression of the transcription factor, IRF-7

PMID: 17544561 According to the classic pathway of type I IFN induction, virus stimulation leads to the phosphorylation of IRF-3, its translocation to the nucleus and subsequent upregulation of a subset of early type I IFN genes.

PMID: 17544561 These IFNs are translated, then secreted, and signal through the IFN-alpha/beta receptor and, through ISGF3 (comprised of STAT1, STAT2 and IRF-9), upregulate IRF-7 expression which is needed for the expression of the full range and magnitude of the IFN-alpha genes.

PMID: 17544561 These IFNs are translated, then secreted, and signal through the IFN-alpha/beta receptor and, through ISGF3 (comprised of STAT1, STAT2 and IRF-9), upregulate IRF-7 expression which is needed for the expression of the full range and magnitude of the IFN-alpha genes.

PMID: 17544561 These IFNs are translated, then secreted, and signal through the IFN-alpha/beta receptor and, through ISGF3 (comprised of STAT1, STAT2 and IRF-9), upregulate IRF-7 expression which is needed for the expression of the full range and magnitude of the IFN-alpha genes.

PMID: 17544561 These IFNs are translated, then secreted, and signal through the IFN-alpha/beta receptor and, through ISGF3 (comprised of STAT1, STAT2 and IRF-9), upregulate IRF-7 expression which is needed for the expression of the full range and magnitude of the IFN-alpha genes.

PMID: 17544561 Proposed candidate receptors for these viral glycoproteins are C-type lectin receptors.

PMID: 17544561 Proposed candidate receptors for these viral glycoproteins are C-type lectin receptors.

PMID: 17544561,9837796,2999320,1850168,7526537, 7908920 In pDC, a requirement for viral envelope glycosylation in IFN-alpha induction, presumably by interaction of the glycoproteins with cell surface receptors, has been demonstrated. Examples of this include the requirement for gD, a glycoprotein of HSV-1 required for viral entry for induction of IFN-alpha in pDC and the mutation of a single amino acid in the M protein of porcine transmissible gastroenteritis virus that renders the virus non-interferogenic and the dependence on gp120 of HIV for IFN induction by pDC

PMID: 17544561,9837796,2999320,1850168,7526537, 7908920 In pDC, a requirement for viral envelope glycosylation in IFN-alpha induction, presumably by interaction of the glycoproteins with cell surface receptors, has been demonstrated. Examples of this include the requirement for gD, a glycoprotein of HSV-1 required for viral entry for induction of IFN-alpha in pDC and the mutation of a single amino acid in the M protein of porcine transmissible gastroenteritis virus that renders the virus non-interferogenic and the dependence on gp120 of HIV for IFN induction by pDC

PMID: 17544561,12900525,15272082,15345224,12470615,15113904,14976261,16224540,15034168 TLR9 is the receptor for both CpG sequences and double-stranded DNA from herpes simplex virus and cytomegalovirus, while the ligands for TLR7 include the imadazoquinolones and single stranded RNA such as found in viruses like HIV-1

PMID: 17544561,16735691 Cao et al. have recently described the expression of the ILT7 receptor on human pDC and demonstrated that it associates with the signal adapter protein Fc¦ÅR1¦Ã to form a receptor complex.

PMID: 17544561, 15767370 A recent study demonstrated that the kinase that interacts with and phosphorylates the IRF-7 is IRAK-1; IRAK-1 deficient mice were found to be severely compromised in their ability to activate IRF-7 and induce type 1 IFN PMID: 17544561, 15815647 MyD88, which is required for signaling through TLR7 and TLR9, forms a complex with IRF-7 that is required for the signaling for type I IFN production in the pDC

PMID: 17544561 They further reported that cross-linking of this receptor on the pDC inhibits CpG and Flu-induced type I IFN and cytokine expression by these cells.

PMID: 17544561 In our study, we demonstrated that IFN-¦Á of PBMC can lead to direct upregulation of CXCL10 in pDC.

PMID: 17544561,17116765 Such activation of CD8+ cells is not always advantageous; for example, it has recently been demonstrated that pDC derived IFN-¦Á can stimulate cytotoxic T cell activity in atherosclerotic plaque through the induction of TRAIL

PMID: 17544561,15815647 MyD88, which is required for signaling through TLR7 and TLR9, forms a complex with IRF-7 that is required for the signaling for type I IFN production in the pDC