The Experts below are selected from a list of 137175 Experts worldwide ranked by ideXlab platform
Robin R Ingalls - One of the best experts on this subject based on the ideXlab platform.
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innate immunity at the mucosal surface role of toll like receptor 3 and toll like receptor 9 in cervical epithelial cell responses to microbial pathogens
Biology of Reproduction, 2006Co-Authors: Jorunn M Andersen, Dina Alkhairy, Robin R IngallsAbstract:Abstract Toll-like receptors (TLRs) are a family of pattern recognition receptors that recognize distinct molecular patterns shared by a broad range of pathogens, including nucleic acids. TLR9, for example, recognizes unmethylated deoxycytidyl-phosphate-deoxyguanosine (CpG) dinucleotides that are common in bacterial and some viral nucleic acids, whereas TLR3 recognizes double-stranded RNA and TLR7/TLR8 recognize single-stranded RNA, which would be found during viral replication. We were interested in whether TLR3, TLR9, and the related TLR9 family members TLR7/TLR8 might play a role in antiviral immune defense at the mucosal epithelial surface of the lower female reproductive tract. We studied cervical epithelial cells and found that they expressed mRNA for TLR3, TLR9, and TLR7, but had only a weak signal for TLR8. For TLR3 and TLR9, protein expression was confirmed to be intracellular. When epithelial cells were incubated with polyinosine-polycytidylic acid and CpG oligodinucleotides, we observed dose-de...
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innate immunity at the mucosal surface role of toll like receptor 3 and toll like receptor 9 in cervical epithelial cell responses to microbial pathogens
Biology of Reproduction, 2006Co-Authors: Jorunn M Andersen, Dina Alkhairy, Robin R IngallsAbstract:Toll-like receptors (TLRs) are a family of pattern recognition receptors that recognize distinct molecular patterns shared by a broad range of pathogens, including nucleic acids. TLR9, for example, recognizes unmethylated deoxycytidyl-phosphate-deoxyguanosine (CpG) dinucleotides that are common in bacterial and some viral nucleic acids, whereas TLR3 recognizes double-stranded RNA and TLR7/TLR8 recognize single-stranded RNA, which would be found during viral replication. We were interested in whether TLR3, TLR9, and the related TLR9 family members TLR7/TLR8 might play a role in antiviral immune defense at the mucosal epithelial surface of the lower female reproductive tract. We studied cervical epithelial cells and found that they expressed mRNA for TLR3, TLR9, and TLR7, but had only a weak signal for TLR8. For TLR3 and TLR9, protein expression was confirmed to be intracellular. When epithelial cells were incubated with polyinosine-polycytidylic acid and CpG oligodinucleotides, we observed dose-dependent upregulation of interleukin-8 secretion. However, cells failed to respond to a variety of TLR7/TLR8 ligands. Polyinosine-polycytidylic acid also induced production of interferon-beta and chemokine C-C motif ligand 5, whereas CpG DNA did not. Cell activation by synthetic oligodinucleotides occurred only in response to the B class sequences, and required the presence of human-specific CpG motifs. In addition, responses to CpG oligodinucleotides could be inhibited by chloroquine, demonstrating the requirement for endosomal maturation. These data demonstrate that mucosal epithelial cells express functional TLR3 and TLR9, and suggest that these receptors play a role in regulating the proinflammatory cytokine and antiviral environment of the lower female reproductive tract during infection with viral and bacterial pathogens.
Jack L Strominger - One of the best experts on this subject based on the ideXlab platform.
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il 10 released by concomitant tlr2 stimulation blocks the induction of a subset of th1 cytokines that are specifically induced by tlr4 or tlr3 in human dendritic cells
Journal of Immunology, 2004Co-Authors: Fabio Re, Jack L StromingerAbstract:Recognition of microbial products through TLRs triggers the expression of several cytokines that regulate innate and adaptive immunity. Signaling by various TLRs is not equivalent and leads to differential gene induction. This study analyzed the responses of human dendritic cells (DCs) and PBMCs stimulated with agonists of TLR2, TLR3, TLR4, TLR5, and TLR7, first individually and then in combination. Several cytokines were equally induced by all TLR agonists, but four genes, IFN-β, IFN-γ-inducible protein 10 (IP-10), IL-12p35, and IL-15, showed a very restricted pattern of induction. Thus, each TLR appears to possess a distinctive ability to activate DCs or PBMCs, suggesting that TLR-mediated responses cannot be simply cataloged as resembling either TLR2 (MyD88 dependent) or TLR4 (MyD88 independent) and that other signaling modalities may exist. The analysis of DC and PBMC activation by combinations of TLR agonists revealed that TLR2 agonists are able to block the induction of IP-10, IL-12p35, and IFN-γ, but not IL-15 and IFN-β, by TLR3 and TLR4. TLR2 stimulation led to rapid release of IL-10 that is responsible for inhibition of IP-10 and IL-12p35 induction. Cross-talk between different TLRs may modify the primary responses of TLR to their agonist, adding a further level of complexity to the regulation of innate immunity.
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il 10 released by concomitant tlr2 stimulation blocks the induction of a subset of th1 cytokines that are specifically induced by tlr4 or tlr3 in human dendritic cells
Journal of Immunology, 2004Co-Authors: Jack L StromingerAbstract:Recognition of microbial products through TLRs triggers the expression of several cytokines that regulate innate and adaptive immunity. Signaling by various TLRs is not equivalent and leads to differential gene induction. This study analyzed the responses of human dendritic cells (DCs) and PBMCs stimulated with agonists of TLR2, TLR3, TLR4, TLR5, and TLR7, first individually and then in combination. Several cytokines were equally induced by all TLR agonists, but four genes, IFN-beta, IFN-gamma-inducible protein 10 (IP-10), IL-12p35, and IL-15, showed a very restricted pattern of induction. Thus, each TLR appears to possess a distinctive ability to activate DCs or PBMCs, suggesting that TLR-mediated responses cannot be simply cataloged as resembling either TLR2 (MyD88 dependent) or TLR4 (MyD88 independent) and that other signaling modalities may exist. The analysis of DC and PBMC activation by combinations of TLR agonists revealed that TLR2 agonists are able to block the induction of IP-10, IL-12p35, and IFN-gamma, but not IL-15 and IFN-beta, by TLR3 and TLR4. TLR2 stimulation led to rapid release of IL-10 that is responsible for inhibition of IP-10 and IL-12p35 induction. Cross-talk between different TLRs may modify the primary responses of TLR to their agonist, adding a further level of complexity to the regulation of innate immunity.
Gunther Hartmann - One of the best experts on this subject based on the ideXlab platform.
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plasmacytoid dendritic cells control tlr7 sensitivity of naive b cells via type i ifn
Journal of Immunology, 2005Co-Authors: Isabelle Beatrice Berkeredjianding, Moritz Wagner, Veit Hornung, Thomas Giese, Max Schnurr, Stefan Endres, Gunther HartmannAbstract:Detailed information of human B cell activation via TLR may lead to a better understanding of B cell involvement in autoimmunity and malignancy. In this study we identified a fundamental difference in the regulation of TLR7- and TLR9-mediated B cell stimulation: whereas the induction of polyclonal naive B cell proliferation by the TLR7 ligands resiquimod (R848) and loxoribine required the presence of plasmacytoid dendritic cells (PDCs), activation via the TLR9 ligand CpG was independent of PDCs. We found that PDC-derived type I IFN enhanced TLR7 sensitivity of B cells by selectively up-regulating TLR7 expression. In contrast the expression levels of TLR9 and of other TLRs studied remained unchanged. In the presence of type I IFN, TLR7 ligation triggered polyclonal B cell expansion and B cell differentiation toward Ig-producing plasma cells; notably, this occurred independently of T cell help and B cell Ag. Human B cells did not respond to ligands of other TLRs including TLR2, TLR4 and TLR6 with and without type I IFN. In conclusion, our results reveal a distinct regulation of TLR7 and TLR9 function in human B cells and highlight TLR7 and TLR9 as unique targets for therapeutic intervention in B cell-mediated immunity and disease.
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quantitative expression of toll like receptor 1 10 mrna in cellular subsets of human peripheral blood mononuclear cells and sensitivity to cpg oligodeoxynucleotides
Journal of Immunology, 2002Co-Authors: Veit Hornung, Thomas Giese, Stefan Endres, Simon Rothenfusser, Stefanie Britsch, Anne Krug, Bernd Jahrsdorfer, Gunther HartmannAbstract:The Toll-like receptor (TLR)9 is critical for the recognition of immunostimulatory CpG motifs but may cooperate with other TLRs. We analyzed TLR1-10 mRNA expression by using quantitative real-time PCR in highly purified subsets of human PBMC and determined the sensitivity of these subsets to CpG oligodeoxynucleotides (ODN). TLR1 and TLR6 were expressed in all cell types examined. TLR10 was highly expressed in B cells and weakly expressed in plasmacytoid dendritic cells (PDC). High expression of TLR2 was characteristic for monocytes. PDC and B cells expressed marked levels of TLR7 and TLR9 and were directly sensitive to CpG ODN. In CpG ODN-stimulated PDC and B cells, TLR9 expression rapidly decreased, as opposed to TLR7, which was up-regulated in PDC and decreased in B cells. In monocytes, NK cells, and T cells, TLR7 was absent. Despite low expression of TLR9, monocytes, NK cells, and T cells did not respond to CpG ODN in the absence of PDC but were activated in the presence of PDC. In conclusion, our studies provide evidence that PDC and B cells, but not monocytes, NK cells, or T cells, are primary targets of CpG ODN in peripheral blood. The characteristic expression pattern of TLR1-10 in cellular subsets of human PBMC is consistent with the concept that TLR9 is essential in the recognition of CpG ODN in PDC and B cells. In addition, selective regulation of TLR7 expression in PDC and B cells by CpG ODN revealed TLR7 as a candidate TLR potentially involved in modulating the recognition of CpG motifs.
Jorunn M Andersen - One of the best experts on this subject based on the ideXlab platform.
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innate immunity at the mucosal surface role of toll like receptor 3 and toll like receptor 9 in cervical epithelial cell responses to microbial pathogens
Biology of Reproduction, 2006Co-Authors: Jorunn M Andersen, Dina Alkhairy, Robin R IngallsAbstract:Abstract Toll-like receptors (TLRs) are a family of pattern recognition receptors that recognize distinct molecular patterns shared by a broad range of pathogens, including nucleic acids. TLR9, for example, recognizes unmethylated deoxycytidyl-phosphate-deoxyguanosine (CpG) dinucleotides that are common in bacterial and some viral nucleic acids, whereas TLR3 recognizes double-stranded RNA and TLR7/TLR8 recognize single-stranded RNA, which would be found during viral replication. We were interested in whether TLR3, TLR9, and the related TLR9 family members TLR7/TLR8 might play a role in antiviral immune defense at the mucosal epithelial surface of the lower female reproductive tract. We studied cervical epithelial cells and found that they expressed mRNA for TLR3, TLR9, and TLR7, but had only a weak signal for TLR8. For TLR3 and TLR9, protein expression was confirmed to be intracellular. When epithelial cells were incubated with polyinosine-polycytidylic acid and CpG oligodinucleotides, we observed dose-de...
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innate immunity at the mucosal surface role of toll like receptor 3 and toll like receptor 9 in cervical epithelial cell responses to microbial pathogens
Biology of Reproduction, 2006Co-Authors: Jorunn M Andersen, Dina Alkhairy, Robin R IngallsAbstract:Toll-like receptors (TLRs) are a family of pattern recognition receptors that recognize distinct molecular patterns shared by a broad range of pathogens, including nucleic acids. TLR9, for example, recognizes unmethylated deoxycytidyl-phosphate-deoxyguanosine (CpG) dinucleotides that are common in bacterial and some viral nucleic acids, whereas TLR3 recognizes double-stranded RNA and TLR7/TLR8 recognize single-stranded RNA, which would be found during viral replication. We were interested in whether TLR3, TLR9, and the related TLR9 family members TLR7/TLR8 might play a role in antiviral immune defense at the mucosal epithelial surface of the lower female reproductive tract. We studied cervical epithelial cells and found that they expressed mRNA for TLR3, TLR9, and TLR7, but had only a weak signal for TLR8. For TLR3 and TLR9, protein expression was confirmed to be intracellular. When epithelial cells were incubated with polyinosine-polycytidylic acid and CpG oligodinucleotides, we observed dose-dependent upregulation of interleukin-8 secretion. However, cells failed to respond to a variety of TLR7/TLR8 ligands. Polyinosine-polycytidylic acid also induced production of interferon-beta and chemokine C-C motif ligand 5, whereas CpG DNA did not. Cell activation by synthetic oligodinucleotides occurred only in response to the B class sequences, and required the presence of human-specific CpG motifs. In addition, responses to CpG oligodinucleotides could be inhibited by chloroquine, demonstrating the requirement for endosomal maturation. These data demonstrate that mucosal epithelial cells express functional TLR3 and TLR9, and suggest that these receptors play a role in regulating the proinflammatory cytokine and antiviral environment of the lower female reproductive tract during infection with viral and bacterial pathogens.
Xuetao Cao - One of the best experts on this subject based on the ideXlab platform.
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shp 2 phosphatase negatively regulates the trif adaptor protein dependent type i interferon and proinflammatory cytokine production
Immunity, 2006Co-Authors: Wei Zhao, Jin Hou, Yan Zhang, Yun Xie, Yuejuan Zheng, Cheng Qian, Jun Zhou, Shuxun Liu, Gensheng Feng, Xuetao CaoAbstract:The Toll-like receptor 3 (TLR3) and TLR4-signaling pathway that involves the adaptor protein TRIF activates type I interferon (IFN) and proinflammatory cytokine expression. Little is known about how TRIF pathway-dependent gene expression is regulated. SH2-containing protein tyrosine phosphatase 2 (SHP-2) is a widely expressed cytoplasmic tyrosine phosphatase. Here we demonstrate that SHP-2 negatively regulated TLR4- and TLR3-activated IFN-beta production. SHP-2 inhibited TLR3-activated but not TLR2-, TLR7-, and TLR9-activated proinflammatory cytokine IL-6 and TNF-alpha production. SHP-2 inhibited poly(I:C)-induced cytokine production by a phosphatase activity-independent mechanism. C-terminal domain of SHP-2 directly bound TANK binding kinase (TBK1) by interacting with the kinase domain of TBK1. SHP-2 deficiency increased TBK1-activated IFN-beta and TNF-alpha expression. TBK1 knockdown inhibited poly(I:C)-induced IL-6 production in SHP-2-deficient cells. SHP-2 also inhibited poly(I:C)-induced activation of MAP kinase pathways. These results demonstrate that SHP-2 specifically negatively regulate TRIF-mediated gene expression in TLR signaling, partially through inhibiting TBK1-activated signal transduction.
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shp 2 phosphatase negatively regulates the trif adaptor protein dependent type i interferon and proinflammatory cytokine production
Immunity, 2006Co-Authors: Wei Zhao, Jin Hou, Yan Zhang, Yun Xie, Yuejuan Zheng, Cheng Qian, Jun Zhou, Shuxun Liu, Gensheng Feng, Xuetao CaoAbstract:Summary The Toll-like receptor 3 (TLR3) and TLR4-signaling pathway that involves the adaptor protein TRIF activates type I interferon (IFN) and proinflammatory cytokine expression. Little is known about how TRIF pathway-dependent gene expression is regulated. SH2-containing protein tyrosine phosphatase 2 (SHP-2) is a widely expressed cytoplasmic tyrosine phosphatase. Here we demonstrate that SHP-2 negatively regulated TLR4- and TLR3-activated IFN-β production. SHP-2 inhibited TLR3-activated but not TLR2-, TLR7-, and TLR9-activated proinflammatory cytokine IL-6 and TNF-α production. SHP-2 inhibited poly(I:C)-induced cytokine production by a phosphatase activity-independent mechanism. C-terminal domain of SHP-2 directly bound TANK binding kinase (TBK1) by interacting with the kinase domain of TBK1. SHP-2 deficiency increased TBK1-activated IFN-β and TNF-α expression. TBK1 knockdown inhibited poly(I:C)-induced IL-6 production in SHP-2-deficient cells. SHP-2 also inhibited poly(I:C)-induced activation of MAP kinase pathways. These results demonstrate that SHP-2 specifically negatively regulate TRIF-mediated gene expression in TLR signaling, partially through inhibiting TBK1-activated signal transduction.
