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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1433-1437.
Prepublished online as a Blood First Edition Paper on October 16, 2003; DOI 10.1182/blood-2003-08-2674.
 Previous Article | Table of Contents | Next Article 
IMMUNOBIOLOGY
Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9
Anne Krug,
Gary D. Luker,
Winfried Barchet,
David A. Leib,
Shizuo Akira, and
Marco Colonna
From the Department of Pathology and Immunology, the Molecular Imaging Center, Mallinckrodt Institute of Radiology, the Departments of Molecular Microbiology, and the Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO; and the Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Japan.
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Abstract
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Natural interferon-producing cells (IPCs) specialize in the production of high levels of type 1 interferons (IFNs) in response to encapsulated DNA and RNA viruses. Here we demonstrate that the secretion of type 1 IFN in response to herpes simplex virus type 1 (HSV-1) in vitro is mediated by the toll-like receptor 9 (TLR9)/MyD88 pathway. Moreover, IPCs produce interleukin-12 (IL-12) in response to HSV-1 in vitro, which is also dependent on TLR9/ MyD88 signaling. Remarkably, though TLR9/MyD88-deficiency abrogates IPC responses to HSV-1 in vitro, mice lacking either MyD88 or TLR9 are capable of controlling HSV-1 replication in vivo after local infection, demonstrating that TLR9- and MyD88-independent pathways in cells other than IPCs can effectively compensate for defective IPC responses to HSV-1.
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Introduction
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Herpes virus simplex type 1 (HSV-1) is a neurotropic  -herpesvirus that causes primary infections of stratified squamous epithelia lining oral mucosa, conjunctiva, cornea, and skin.1 During primary infection, HSV-1 infects the adjacent sensory neuron endings and reaches the sensory ganglia, where it persists in a latent state. Sporadically, HSV-1 is reactivated and travels from the sensory neurons back to the epithelial tissue. Reactivation can cause tissue damage from the cytopathic infection of epithelial cells and inflammation. In immunocompetent hosts, HSV-1 infection triggers the secretion of interferon- (IFN-), which has a critical function in host anti–HSV-1 response.2,3 IFN- inhibits the transcription of immediate-early HSV-1 genes.4 In mice IFN- is a potent inhibitor of HSV-1 replication in the cornea,5 and it activates host defenses such as natural killer cells, which participate in controlling HSV-1 infection and disease.6 IFN- has also been shown to limit the progress of infection from peripheral tissues to the nervous system.7 It has been proposed that the IFN- response to HSV-1 is triggered by recognition of the HSV-1 envelope glycoprotein D (gD).8 Dendritic cells (DCs) may bind HSV-1 glycoproteins through the mannose receptor and possibly other lectins.9 CC-chemokine receptor 3 (CCR3) or CXC-chemokine receptor 4 (CXCR4) may function as coreceptors.8 The intracellular events linking the recognition of HSV-1 glycoproteins with IFN- secretion are unknown.
As does bacterial DNA, HSV-1 DNA contains abundant deoxycytidylate-phosphate-deoxyguanylate (CpG) motifs.10 These motifs stimulate multiple cellular components of the immune system through the recently characterized toll-like receptor 9 (TLR9).11-14 TLR9 transduces intracellular signals through myeloid differentiation factor 88 (MyD88), which initiates a signaling cascade leading to NF- B activation and cytokine secretion.15,16 Thus, TLR9 might provide another pathway that links HSV-1 recognition with IFN- responses. To test this hypothesis we focused on natural interferon-producing cells (IPC). IPCs, also called plasmacytoid dendritic cells (pDCs), respond to HSV-1 and to other DNA and RNA viruses by secreting high levels of IFN-, - , and - ,17-23 releasing IL-1222,24,25 and up-regulating costimulatory molecules.22,24-26 Human and murine IPCs express TLR9 and are activated by single-stranded oligodeoxynucleotides (ODNs) containing CpG motifs.14,27-31 Thus, they represent a valuable biologic system to test the role of TLR9 in immune cell responses to HSV-1. Here we demonstrate that IPC responsiveness to HSV-1 in vitro is indeed mediated by the TLR9/MyD88 pathway. However, mice lacking either MyD88 or TLR9 can control HSV-1 replication after local infection, demonstrating that TLR9- and MyD88-independent mechanisms can effectively compensate for impaired anti–HSV-1 IPC responses in vivo.
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Materials and methods
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Isolation and culture of IPCs and DCs, flow cytometric analyses, and determination of cytokine secretion
MyD88–/– mice32 were backcrossed to C57BL/6, and TLR9–/– mice13 were backcrossed to BALB/c. Mice were between 6 and 12 weeks of age. Spleen DCs were isolated with CD11c+ microbeads (Miltenyi Biotec, Bergisch-Gladbach, Germany). IPCs (CD11c+/Ly-6C+/CD11b– cells), CD11b+ DCs (CD11c+/Ly-6C–/CD11b+ cells, which comprise myeloid DCs), and CD11b– DCs (CD11c+/Ly-6C–/CD11b– cells, which comprise CD8+ DCs) were sorted from CD11c+ splenocytes using a MoFlo cytometer (Cytomation, Fort Collins, CO; more than 95% purity), as previously described.33 Bone marrow–derived IPCs were generated from bone marrow cells by culture with human recombinant fms-related tyrosine kinase 3 ligand (Flt3L) (10 ng/mL; R&D Systems, Minneapolis, MN) for 7 days and were purified by sorting the CD11c+/CD11blow population as described.33 Cells were cultured with purified KOS HSV-1 (0.01-10 multiplicity of infection [MOI]), CpG ODN 2216 (3 µg/mL; Qiagen, Valencia, CA) or influenza virus PR8 (1 MOI) for 36 hours at the indicated cell density.33 Ultraviolet (UV)–inactivation of diluted HSV-1 stock (5 x 106 and 5 x 105 plaque-forming units (PFU)/mL) was performed using a UV crosslinker (optimal crosslink setting, 1.2 x 105 µJ/cm2).34 IFN- and IL-12 in culture supernatants were measured using enzyme-linked immunosorbent assay (ELISA; PBL Biomedical Laboratories, New Brunswick, NJ and BD Biosciences, Franklin Lakes, NJ). The IFN- ELISA detects IFN-A, 1, 4, 5, 6, and 9 subspecies. Expression of CD86 was determined by flow cytometry33 and is shown as median fluorescence intensity. The median value of the isotype control is indicated in the figures as a dashed line.
Recombinant virus and bioluminescence imaging of HSV-1 infection
To detect HSV-1 replication in living mice, we used a KOS HSV-1 recombinant strain, KOS/Dlux/oriL, which expresses the firefly luciferase (FL) reporter protein.35 KOS/Dlux/oriL was constructed by homologous recombination into a site between UL49 and UL50, with a cassette encoding the UL30 promoter to regulate FL as described previously.36 HSV-1 was injected in the footpads of 6- to 12-week-old (approximate ages) mice (2 x 106 or 107 PFU/footpad as indicated). Viral infection in mouse footpads was detected by bioluminescence imaging of FL using a cooled charge-coupled device camera (IVIS; Xenogen, Cranbury, NJ). Bioluminescence imaging was repeated every 24 hours for 1 week. Signal intensities from regions of interest were expressed as total photon flux (photons per second).
Corneal infection model and HSV-1 plaque assay
Corneal infection, eye swabs, and excision of trigeminal ganglia were performed as described previously.37 Briefly, mice were infected with 2 x 106 PFU per eye after scarification of the corneas. Eye swabs were taken at the indicated time points and diluted in 1 mL culture medium. Trigeminal ganglia were homogenized in 1 mL culture medium. Viral titers were determined by standard plaque assay on Vero cells and are presented as logarithmic mean ± SD of plaque-forming units per milliliter. The limit of detection was 10 PFU/mL.
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Results
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IFN- and IL-12 responses of IPCs to HSV-1 are impaired in MyD88-deficient mice
CD11c+ splenocytes were isolated from MyD88-deficient and control mice and were cultured in vitro with HSV-1. After 36 hours, IFN- and IL-12 in culture supernatants were quantified using ELISA. As shown in Figure 1A, MyD88-deficient CD11c+ splenocytes secreted considerably less IFN- and IL-12 than did wild-type DCs in response to HSV-1. CD11c+ splenocytes include IPCs, which represent a major source of IFN- and IL-12.22 In addition, they include CD11b+ DCs and CD11b– DCs, which are also capable of secreting cytokines when exposed to appropriate bacterial and viral stimuli.38,39 Therefore, we asked whether these cell subsets respond to HSV-1 in a MyD88-dependent fashion. IPCs, CD11b+ DCs, and CD11b– DCs were sorted from MyD88–/– and control mice and were stimulated in vitro with HSV-1 to induce the secretion of IFN- and IL-12. As shown in Figure 1B, wild-type IPCs secreted large amounts of IFN- and IL-12, whereas cytokine secretion of MyD88–/– IPCs was severely impaired. Wild-type CD11b+ and CD11b– DCs secreted significant levels of IL-12 but very low levels of IFN- in response to HSV-1. These responses were reduced in MyD88–/– DCs. Finally, we investigated the impact of MyD88 deficiency on the response of IPCs derived from bone marrow precursors to HSV-1. As shown in Figure 1C, the secretion of IFN- and IL-12 and the up-regulation of CD86 were negligible in MyD88–/– bone marrow–derived IPCs compared to normal IPCs (Figure 1C). We conclude that MyD88 is essential for the IFN- and IL-12 responses of primary IPCs and DC and of bone marrow–derived IPCs to HSV-1 in vitro.
IPC responses to HSV-1 are mediated by TLR9 and do not require viral replication
All murine IPCs and DCs express TLR9,30,31 which signals exclusively through MyD88.15,16 Thus, MyD88-dependent responses of IPCs and DCs to HSV-1 may be initiated by TLR9. To test this hypothesis, we prepared total CD11c+ splenocytes, IPCs, CD11b+ DCs, CD11b– DCs, and bone marrow–derived IPCs from TLR9-deficient mice and tested their responses to HSV-1. As shown in Figure 2, TLR9-deficient CD11c+ splenocytes, primary IPCs, and bone marrow–derived IPCs secreted significantly less IFN- and IL-12 than did their wild-type counterparts. Upregulation of CD86 in response to HSV-1 was also reduced in TLR9-deficient IPCs in comparison with wild-type IPCs, although this marker of activation was less disrupted than cytokine secretion (Figure 2C). Remarkably, IPC responses to influenza virus (strain PR8) were intact in TLR9–/– mice, indicating that IPC recognition of influenza virus is TLR9 independent. Wild-type DCs secreted some IL-12 but no IFN-, whereas TLR9–/– DCs did not respond to HSV-1 at all. To further corroborate the evidence that TLR9 mediates IPC responses to HSV-1, we cultured wild-type bone marrow–derived IPCs in vitro with HSV-1 either in the presence or the absence of ODN 2088, a competitive inhibitor of TLR9.40 As shown in Figure 3, ODN 2088 inhibited the wild-type IPC secretion of IFN- and IL-12 and the up-regulation of CD86 in a dose-dependent fashion. ODN 2088 had little effect on IPC responses to influenza virus, demonstrating that ODN 2088 selectively inhibited TLR9-mediated responses, further confirming that recognizing influenza virus is TLR9 independent. We conclude that IPC responses to HSV-1 are critically dependent on TLR9. Finally, we tested whether IPC responses to HSV-1 through TLR9/MyD88 require active viral replication. HSV-1 was treated with UV light to prevent viral replication without denaturing envelope glycoproteins. UV-inactivated HSV-1 was as potent as untreated virus in inducing IFN- and IL-12 production by bone marrow–derived IPCs (Figure 4) and IPCs sorted from CD11c+ splenocytes (not shown). Thus, IPC responses to HSV-1 in vitro occur in the absence of viral replication.
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Figure 3.. Inhibition of cytokine production and costimulatory molecule expression by TLR9 antagonist CpG ODN 2088. Bone marrow–derived IPCs (5 x 105 cells/mL, 129/SvJ strain) were preincubated with increasing doses of the competitive TLR9 antagonist CpG ODN 2088 (0.04-2.5 µM) and then were cultured with HSV-1 (5 MOI), influenza virus PR8 (1 MOI), or medium alone for 24 hours. IFN- and IL-12 were measured in the supernatants using ELISA. CD86 expression was determined by flow cytometry and is expressed as median fluorescence intensity after subtracting the background of the isotype control.
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Mice lacking MyD88 or TLR9 can control HSV-1 replication after local infection in vivo
Finally, we investigated the impact of MyD88- and TLR9-mediated responses on HSV-1 replication in vivo. To monitor HSV-1 replication in living animals, we infected mice with KOS/Dlux/oriL HSV-1 strain that expresses the firefly luciferase reporter protein, allowing visualization of HSV-1 replication by bioluminescence imaging.35 After footpad injection, HSV-1 replication was monitored in MyD88–/– mice, TLR9–/– mice, and control mice with a charge-coupled device camera every 24 hours for 6 to 7 days. In all mice, HSV-1 replication was detected exclusively at the site of infection (Figure 5A-D). Replication was sustained up to approximately day 4 or 5 after infection, and then it declined progressively (Figure 5E-F). Measuring photon flux at the site of infection revealed slightly more HSV-1 replication in MyD88–/– mice than in wild-type mice (Figure 5A-B, E). However, no significant difference was detected between TLR9–/– and wild-type mice (Figure 5C-D, F). No systemic spreading of HSV-1, signs of paralysis, or death were detected in MyD88–/– or TLR9–/– mice. It could be argued that bioluminescence imaging is not sensitive enough to detect small differences in HSV-1 replication between wild-type and TLR9/MyD88-deficient mice or that the KOS/Dlux/oriL HSV-1 may be slightly attenuated compared with the unaltered KOS HSV-1. To address this possibility, wild-type and MyD88–/– mice were infected with KOS HSV-1 by corneal scarification, and viral titers were determined in eye swabs and homogenized trigeminal ganglia by standard plaque assay. As shown in Figure 5, panels G and H, HSV-1 replication was not increased in MyD88–/– mice compared with wild-type mice. We conclude that TLR9/MyD88-independent mechanisms can effectively compensate for the absence of TLR9 or MyD88 during an in vivo immune response against localized HSV-1 infection.
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Figure 5.. Replication of HSV-1 in MyD88–/–, TLR9–/–, and control mice. (A-B, E) MyD88–/– and C57BL/6 control mice (8-week-old males; n = 6) were injected with 107 PFU KOS/Dlux/OriL HSV-1 in each hind footpad. (C-D, F) TLR9–/– and Balb/c controls (6- to 7-week-old males; n = 5) were injected with 2 x 106 PFU KOS/Dlux/OriL HSV-1 in each hind footpad. Viral replication and spatial distribution of replicating virus was visualized by bioluminescence imaging daily up to day 7. Representative images taken 24 hours and 6 days after infection are shown (A-D). Signal intensities from hind feet were measured as photon flux (photons/second) within defined regions of interest (E-F). Mean values ± SEM are shown for each time point. (G-H) C57BL/6J wild-type and MyD88–/– mice were infected with 2 x 106 PFU KOS HSV-1 in each eye after corneal scarification. Viral titers of eye swabs (G) and trigeminal ganglia (H) were measured by plaque assay at different time points. Logarithmic mean values ± SD are shown (n = 3).
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Discussion
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In this study, we investigated the mechanisms of IPC activation by HSV-1. Our results demonstrate that HSV-1 activates IPC in vitro mainly through the TLR9/MyD88 pathway. In agreement with this conclusion, TLR9- and MyD88-deficient IPCs have severely impaired responses to HSV-1, including dramatically reduced secretion of IFN- and IL-12 and significantly decreased cell activation. Moreover, blocking TLR9 in wild-type IPCs with an inhibitory CpG ODN had comparable consequences. How does TLR9 recognize HSV-1? UV-inactivated HSV-1 stimulated IPC responses just as untreated HSV-1 did, indicating that HSV-1 replication is not required for the effective stimulation of TLR9/MyD88. Because TLR9 is located in an intracellular endosomal compartment,41 HSV-1 may initially interact with cell surface receptors specific for envelope glycoproteins. After the internalization of encapsulated HSV-1, viral DNA may be released in an endosomal compartment for interaction with TLR9. Thus, IPCs emerge as unique sentinel cells that sense and respond to HSV-1 without becoming productively infected. This conclusion is consistent with the recent demonstration that IPCs recognize HSV-2 through TLR942 and that UV-inactivated HSV-2 and HSV-2 DNAs are sufficient to activate IPCs, whereas a pharmacologic inhibitor of endosomal-lysosomal processing blocks activation.42 Together these studies suggest that other DNAviruses may activate IPCs through the same pathway. Notably, our study also demonstrates that IPCs are major producers of IL-12 in response to HSV-1. IL-12 secretion by IPC and classical DC subsets is also dependent on TLR9/MyD88 signaling, consistent with previous reports that TLR9 is expressed in all murine DC subsets.30,31 It remains unclear why HSV-1 is more effective in stimulating IFN- responses of IPCs than of DCs. HSV-1 may inhibit DC maturation, as observed in human DCs infected by HSV-1,43 or it may selectively block the TLR9/MyD88 pathway in DCs, as previously reported for the RNaseL and protein kinase regulated by RNA (PKR) pathways, which also mediate host resistance to HSV-1.37,44
Despite the dramatic effect of MyD88 and TLR9 deficiencies on IPC secretion of IFN- and IL-12 in vitro, we detected no significant increase of HSV-1 replication in MyD88–/– and TLR9–/– mice compared with wild-type mice using the bioluminescent KOS/Dlux/oriL HSV-1 strain. Similarly, the replication of KOS HSV-1 after corneal infection was not greater in MyD88–/– mice than in wild-type mice, as assessed using a standard plaque assay. Moreover, no neurologic symptoms or systemic spreading of HSV-1 was observed in MyD88- or TLR9-deficient mice, even after footpad injection of 5 x 107 PFU of KOS HSV-1 (data not shown). Thus, MyD88 and TLR9 deficiencies had limited or no impact on host ability to control HSV-1 replication in our model of local infection.
In conclusion, our study indicates that TLR9/MyD88-independent responses of cells other than IPCs can mostly compensate for the lack of TLR9/MyD88-dependent responses of IPCs in local HSV-1 infections. Epithelial cells, fibroblasts, macrophages, or other immune cells infiltrating HSV-1–infected skin and mucosa may efficiently recognize and respond to HSV-1 through TLR9/MyD88-independent pathways. These pathways may be initiated by the mannose receptor,9 the chemokine receptors,8 or the herpesvirus entry mediator, which activates nuclear factor-kappa B (NF-B) and activator protein-1 (AP-1) transcription factors.45,46 Intracellular replication of HSV-1 may also generate double-stranded (ds) RNA products that activate dsRNA-dependent PKR,47 leading to the activation of IRF3 and the expression of IFN type 1.48 Finally, HSV-1 could activate the recently discovered TRIF pathway downstream of TLR3 or TLR4, inducing IFN- secretion sufficient to control viral replication.49,50 IPCs and the TLR9/MyD88 pathway may become relevant in IFN- responses to viruses that access the bloodstream and cause systemic infections in vivo.
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Acknowledgements
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We thank Akiko Iwasaki (Yale University) for sharing unpublished results, Arthur M. Krieg (Coley Pharmaceutical Group, Wellesley, MA) for providing TLR9–/– mice, Kathy Frederick and Emil R. Unanue (Washington University) for MyD88–/– mice, William Eades (Siteman Cancer Center flow cytometry facility) for expert cell sorting, and Marina Cella and Susan Gilfillan (Washington University) for advice and helpful discussions.
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Footnotes
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Submitted August 5, 2003;
accepted October 9, 2003.
Prepublished online as Blood First Edition Paper, October 16, 2003; DOI 10.1182/blood-2003-08-2674.
Supported by the Deutsche Forschungsgemeinschaft (KR 2199/1-1) (A.K.), RO1 EY09083 (D.A.L.), and a Research to Prevent Blindness Lew Wasserman Scholarship (D.A.L.). Supported also by National Institutes of Health grant PA CA94056 awarded to the Molecular Imaging Center.
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734.
Reprints: Marco Colonna, Department of Pathology and Immunology, Washington University School of Medicine, Box 8118, 660 S Euclid Ave, St Louis, MO 63110; e-mail: mcolonna{at}pathology.wustl.edu.
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References
|
|---|
- Whitley RJ. Fields Virology. In: Knipe DM, Howley PM, eds. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.
- Tan SL, Katze MG. HSV.com: maneuvering the internetworks of viral neuropathogenesis and evasion of the host defense. Proc Natl Acad Sci U S A. 2000;97: 5684-5686.[Free Full Text]
- Katze MG, He Y, Gale M Jr. Viruses and interferon: a fight for supremacy. Nat Rev Immunol. 2002;2: 675-687.[CrossRef][Medline]
[Order article via Infotrieve]
- Oberman F, Panet A. Inhibition of transcription of herpes simplex virus immediate early genes in interferon-treated human cells. J Gen Virol. 1988; 69(pt 6): 1167-1177.[Abstract/Free Full Text]
- Hendricks RL, Weber PC, Taylor JL, Koumbis A, Tumpey TM, Glorioso JC. Endogenously produced interferon alpha protects mice from herpes simplex virus type 1 corneal disease. J Gen Virol. 1991;72(pt 7): 1601-1610.[Abstract/Free Full Text]
- Bouley DM, Kanangat S, Rouse BT. The role of the innate immune system in the reconstituted SCID mouse model of herpetic stromal keratitis. Clin Immunol Immunopathol. 1996;80: 23-30.[CrossRef][Medline]
[Order article via Infotrieve]
- Halford WP, Veress LA, Gebhardt BM, Carr DJ. Innate and acquired immunity to herpes simplex virus type 1. Virology. 1997;236: 328-337.[CrossRef][Medline]
[Order article via Infotrieve]
- Ankel H, Westra DF, Welling-Wester S, Lebon P. Induction of interferon-alpha by glycoprotein D of herpes simplex virus: a possible role of chemokine receptors. Virology. 1998;251: 317-326.[CrossRef][Medline]
[Order article via Infotrieve]
- Milone MC, Fitzgerald-Bocarsly P. The mannose receptor mediates induction of IFN- in peripheral blood dendritic cells by enveloped RNA and DNA viruses. J Immunol. 1998;161: 2391-2399.[Abstract/Free Full Text]
- Zheng M, Klinman DM, Gierynska M, Rouse BT. DNA containing CpG motifs induces angiogenesis. Proc Natl Acad Sci U S A. 2002;99: 8944-8949.[Abstract/Free Full Text]
- Krieg AM. CpG motifs in bacterial DNA and their immune effects. Annu Rev Immunol. 2002;20: 709-760.[CrossRef][Medline]
[Order article via Infotrieve]
- Medzhitov R. Toll-like receptors and innate immunity. Nat Rev Immunol. 2001;1: 135-145.[CrossRef][Medline]
[Order article via Infotrieve]
- Hemmi H, Takeuchi O, Kawai T, et al. A Toll-like receptor recognizes bacterial DNA. Nature. 2000; 408: 740-745.[CrossRef][Medline]
[Order article via Infotrieve]
- Bauer S, Kirschning CJ, Hacker H, et al. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc Natl Acad Sci U S A. 2001;98: 9237-9242.[Abstract/Free Full Text]
- Hacker H, Vabulas RM, Takeuchi O, Hoshino K, Akira S, Wagner H. Immune cell activation by bacterial CpG-DNA through myeloid differentiation marker 88 and tumor necrosis factor receptor-associated factor (TRAF)6. J Exp Med. 2000; 192: 595-600.[Abstract/Free Full Text]
- Schnare M, Holt AC, Takeda K, Akira S, Medzhitov R. Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88. Curr Biol. 2000;10: 1139-1142.[CrossRef][Medline]
[Order article via Infotrieve]
- Perussia B, Fanning V, Trinchieri G. A leukocyte subset bearing HLA-DR antigens is responsible for in vitro alpha interferon production in response to viruses. Nat Immun Cell Growth Regul. 1985;4: 120-137.[Medline]
[Order article via Infotrieve]
- Fitzgerald-Bocarsly P, Feldman M, Mendelsohn M, Curl S, Lopez C. Human mononuclear cells which produce interferon-alpha during NK(HSV-FS) assays are HLA-DR positive cells distinct from cytolytic natural killer effectors. J Leukoc Biol. 1988;43: 323-334.[Abstract]
- Ronnblom L, Cederblad B, Sandberg K, Alm GV. Determination of herpes simplex virus-induced alpha interferon-secreting human blood leucocytes by a filter immuno-plaque assay. Scand J Immunol. 1988;27: 165-170[CrossRef][Medline]
[Order article via Infotrieve]
- Siegal FP, Kadowaki N, Shodell M, et al. The nature of the principal type 1 interferon-producing cells in human blood. Science. 1999;284: 1835-1837.[Abstract/Free Full Text]
- Cella M, Jarrossay D, Facchetti F, et al. Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat Med. 1999;5: 919-923.[CrossRef][Medline]
[Order article via Infotrieve]
- Asselin-Paturel C, Boonstra A, Dalod M, et al. Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology. Nat Immunol. 2001;2: 1144-1150.[CrossRef][Medline]
[Order article via Infotrieve]
- Feldman SB, Ferraro M, Zheng HM, Patel N, Gould-Fogerite S, Fitzgerald-Bocarsly P. Viral induction of low frequency interferon-alpha producing cells. Virology. 1994;204: 1-7.[CrossRef][Medline]
[Order article via Infotrieve]
- Cella M, Facchetti F, Lanzavecchia A, Colonna M. Plasmacytoid dendritic cells activated by influenza virus and CD40L drive a potent TH1 polarization. Nat Immunol. 2000;1: 305-310.[CrossRef][Medline]
[Order article via Infotrieve]
- Dalod M, Salazar-Mather TP, Malmgaard L, et al. Interferon alpha/beta and interleukin 12 responses to viral infections: pathways regulating dendritic cell cytokine expression in vivo. J Exp Med. 2002;195: 517-528.[Abstract/Free Full Text]
- Fonteneau JF, Gilliet M, Larsson M, et al. Activation of influenza virus-specific CD4+ and CD8+ T cells: a new role for plasmacytoid dendritic cells in adaptive immunity. Blood. 2003;101: 3520-3526.[Abstract/Free Full Text]
- Jarrossay D, Napolitani G, Colonna M, Sallusto F, Lanzavecchia A. Specialization and complementarity in microbial molecule recognition by human myeloid and plasmacytoid dendritic cells. Eur J Immunol. 2001;31: 3388-3393.[CrossRef][Medline]
[Order article via Infotrieve]
- Kadowaki N, Ho S, Antonenko S, et al. Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J Exp Med. 2001;194: 863-869.[Abstract/Free Full Text]
- Krug A, Towarowski A, Britsch S, et al. Toll-like receptor expression reveals CpG DNA as a unique microbial stimulus for plasmacytoid dendritic cells which synergizes with CD40 ligand to induce high amounts of IL-12. Eur J Immunol. 2001;31: 3026-3037.[CrossRef][Medline]
[Order article via Infotrieve]
- Edwards AD, Diebold SS, Slack EM, et al. Toll-like receptor expression in murine DC subsets: lack of TLR7 expression by CD8 alpha+ DC correlates with unresponsiveness to imidazoquinolines. Eur J Immunol. 2003;33: 827-833.[CrossRef][Medline]
[Order article via Infotrieve]
- Boonstra A, Asselin-Paturel C, Gilliet M, et al. Flexibility of mouse classical and plasmacytoid-derived dendritic cells in directing T helper type 1 and 2 cell development: dependency on antigen dose and differential toll-like receptor ligation. J Exp Med. 2003;197: 101-109.[Abstract/Free Full Text]
- Adachi O, Kawai T, Takeda K, et al. Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function. Immunity. 1998;9: 143-150.[CrossRef][Medline]
[Order article via Infotrieve]
- Krug A, Veeraswamy R, Pekosz A, et al. Interferon-producing cells fail to induce proliferation of naive T cells but can promote expansion and T helper 1 differentiation of antigen-experienced unpolarized T cells. J Exp Med. 2003;197: 899-906.[Abstract/Free Full Text]
- Eloranta ML, Alm GV. Splenic marginal metallophilic macrophages and marginal zone macrophages are the major interferon-alpha/beta producers in mice upon intravenous challenge with herpes simplex virus. Scand J Immunol. 1999;49: 391-394.[CrossRef][Medline]
[Order article via Infotrieve]
- Luker GD, Bardill JP, Prior JL, Pica CM, Piwnica-Worms D, Leib DA. Noninvasive bioluminescence imaging of herpes simplex virus type 1 infection and therapy in living mice. J Virol. 2002;76: 12149-12161.[Abstract/Free Full Text]
- Summers BC, Leib DA. Herpes simplex virus type 1 origins of DNA replication play no role in the regulation of flanking promoters. J Virol. 2002; 76: 7020-7029.[Abstract/Free Full Text]
- Leib DA, Harrison TE, Laslo KM, Machalek MA, Moorman NJ, Virgin HW. Interferons regulate the phenotype of wild-type and mutant herpes simplex viruses in vivo. J Exp Med. 1999;189: 663-672.[Abstract/Free Full Text]
- Maldonado-Lopez R, De Smedt T, Michel P, et al. CD8+ and CD8– subclasses of dendritic cells direct the development of distinct T helper cells in vivo. J Exp Med. 1999;189: 587-592.[Abstract/Free Full Text]
- Diebold SS, Montoya M, Unger H, et la. Viral infection switches non-plasmacytoid dendritic cells into high interferon producers [abstract]. Nature. 2003;424: 324.[CrossRef][Medline]
[Order article via Infotrieve]
- Stunz LL, Lenert P, Peckham D, et al. Inhibitory oligonucleotides specifically block effects of stimulatory CpG oligonucleotides in B cells. Eur J Immunol. 2002;32: 1212-1222.[CrossRef][Medline]
[Order article via Infotrieve]
- Ahmad-Nejad P, Hacker H, Rutz M, Bauer S, Vabulas RM, Wagner H. Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments. Eur J Immunol. 2002;32: 1958-1968.[CrossRef][Medline]
[Order article via Infotrieve]
- Lund J, Sato A, Akira S, Medzhitov R, Iwasaki A. Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells. J Exp Med. 2003;198: 513-520.[Abstract/Free Full Text]
- Salio M, Cella M, Suter M, Lanzavecchia A. Inhibition of dendritic cell maturation by herpes simplex virus. Eur J Immunol. 1999;29: 3245-3253.[CrossRef][Medline]
[Order article via Infotrieve]
- Chou J, Chen JJ, Gross M, Roizman B. Association of a M(r) 90,000 phosphoprotein with protein kinase PKR in cells exhibiting enhanced phosphorylation of translation initiation factor eIF-2 alpha and premature shutoff of protein synthesis after infection with gamma 134.5- mutants of herpes simplex virus 1. Proc Natl Acad Sci U S A. 1995;92: 10516-10520.[Abstract/Free Full Text]
- Hsu H, Solovyev I, Colombero A, Elliott R, Kelley M, Boyle WJ. ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5. J Biol Chem. 1997;272: 13471-13474.[Abstract/Free Full Text]
- Marsters SA, Ayres TM, Skubatch M, Gray CL, Rothe M, Ashkenazi A. Herpesvirus entry mediator, a member of the tumor necrosis factor receptor (TNFR) family, interacts with members of the TNFR-associated factor family and activates the transcription factors NF-B and AP-1. J Biol Chem. 1997;272: 14029-14032.[Abstract/Free Full Text]
- Meurs E, Chong K, Galabru J, et al. Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon. Cell. 1990;62: 379-390.[CrossRef][Medline]
[Order article via Infotrieve]
- Juang YT, Lowther W, Kellum M, et al. Primary activation of interferon A and interferon B gene transcription by interferon regulatory factor 3. Proc Natl Acad Sci U S A. 1998;95: 9837-9842.[Abstract/Free Full Text]
- Yamamoto M, Sato S, Hemmi H, et al. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science. 2003;301: 640-643.[Abstract/Free Full Text]
- Hoebe K, Du X, Georgel P, et al. Identification of Lps2 as a key transducer of MyD88-independent TIR signalling. Nature. 2003;424: 743-748.[CrossRef][Medline]
[Order article via Infotrieve]
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[Full Text]
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|
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|
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[Full Text]
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[Full Text]
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[Full Text]
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|
|
|
|
|
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|
|
|
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|
|
|
|
|
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|
|
|
|
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|
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2208 - 2217.
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|
|
|
|
|
|
|
A. J. Currie, R. G. van der Most, S. A. Broomfield, A. C. Prosser, M. G. Tovey, and B. W. S. Robinson
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180(3):
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|
|
|
|
|
|
|
S. Guggemoos, D. Hangel, S. Hamm, A. Heit, S. Bauer, and H. Adler
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180(1):
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|
|
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M. C. Silva, A. Guerrero-Plata, F. D. Gilfoy, R. P. Garofalo, and P. W. Mason
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|
|
|
|
|
|
|
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[Full Text]
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|
|
|
|
|
|
|
S. Varani, M. Cederarv, S. Feld, C. Tammik, G. Frascaroli, M. P. Landini, and C. Soderberg-Naucler
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Waibler, M. Anzaghe, H. Ludwig, S. Akira, S. Weiss, G. Sutter, and U. Kalinke
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81(22):
12102 - 12110.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. L. Hokeness-Antonelli, M. J. Crane, A. M. Dragoi, W.-M. Chu, and T. P. Salazar-Mather
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J. Immunol.,
November 1, 2007;
179(9):
6176 - 6183.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. P. Sarangi, B. Kim, E. Kurt-Jones, and B. T. Rouse
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J. Virol.,
October 15, 2007;
81(20):
11128 - 11138.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. J. Martin, J. M. Lee, D. Walls, and S. D. Hayward
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J. Virol.,
September 15, 2007;
81(18):
9748 - 9758.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Weslow-Schmidt, N. A. Jewell, S. E. Mertz, J. P. Simas, J. E. Durbin, and E. Flano
Type I Interferon Inhibition and Dendritic Cell Activation during Gammaherpesvirus Respiratory Infection
J. Virol.,
September 15, 2007;
81(18):
9778 - 9789.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Lore, W. C. Adams, M. Havenga, M. L. Precopio, L. Holterman, J. Goudsmit, and R. A. Koup
Myeloid and Plasmacytoid Dendritic Cells Are Susceptible to Recombinant Adenovirus Vectors and Stimulate Polyfunctional Memory T Cell Responses
J. Immunol.,
August 1, 2007;
179(3):
1721 - 1729.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Magnusson, R. Tobes, J. Sancho, and E. Pareja
Cutting Edge: Natural DNA Repetitive Extragenic Sequences from Gram-Negative Pathogens Strongly Stimulate TLR9
J. Immunol.,
July 1, 2007;
179(1):
31 - 35.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Uematsu and S. Akira
Toll-like Receptors and Type I Interferons
J. Biol. Chem.,
May 25, 2007;
282(21):
15319 - 15323.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Nociari, O. Ocheretina, J. W. Schoggins, and E. Falck-Pedersen
Sensing Infection by Adenovirus: Toll-Like Receptor-Independent Viral DNA Recognition Signals Activation of the Interferon Regulatory Factor 3 Master Regulator
J. Virol.,
April 15, 2007;
81(8):
4145 - 4157.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. M. Guay, T. A. Andreyeva, R. L. Garcea, R. M. Welsh, and E. Szomolanyi-Tsuda
MyD88 Is Required for the Formation of Long-Term Humoral Immunity to Virus Infection
J. Immunol.,
April 15, 2007;
178(8):
5124 - 5131.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Zhou, E. A. Kurt-Jones, K. A. Fitzgerald, J. P. Wang, A. M. Cerny, M. Chan, and R. W. Finberg
Role of MyD88 in Route-Dependent Susceptibility to Vesicular Stomatitis Virus Infection
J. Immunol.,
April 15, 2007;
178(8):
5173 - 5181.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Wang, D. R. Asher, M. Chan, E. A. Kurt-Jones, and R. W. Finberg
Cutting Edge: Antibody-Mediated TLR7-Dependent Recognition of Viral RNA
J. Immunol.,
March 15, 2007;
178(6):
3363 - 3367.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. K. Lee, J. M. Lund, B. Ramanathan, N. Mizushima, and A. Iwasaki
Autophagy-Dependent Viral Recognition by Plasmacytoid Dendritic Cells
Science,
March 9, 2007;
315(5817):
1398 - 1401.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Iacobelli-Martinez and G. R. Nemerow
Preferential Activation of Toll-Like Receptor Nine by CD46-Utilizing Adenoviruses
J. Virol.,
February 1, 2007;
81(3):
1305 - 1312.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Koizumi, T. Yamaguchi, K. Kawabata, F. Sakurai, T. Sasaki, Y. Watanabe, T. Hayakawa, and H. Mizuguchi
Fiber-Modified Adenovirus Vectors Decrease Liver Toxicity through Reduced IL-6 Production
J. Immunol.,
February 1, 2007;
178(3):
1767 - 1773.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kawai and S. Akira
Antiviral Signaling Through Pattern Recognition Receptors
J. Biochem.,
February 1, 2007;
141(2):
137 - 145.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Lund, M. M. Linehan, N. Iijima, and A. Iwasaki
Cutting Edge: Plasmacytoid Dendritic Cells Provide Innate Immune Protection against Mucosal Viral Infection In Situ
J. Immunol.,
December 1, 2006;
177(11):
7510 - 7514.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Paladino, D. T. Cummings, R. S. Noyce, and K. L. Mossman
The IFN-Independent Response to Virus Particle Entry Provides a First Line of Antiviral Defense That Is Independent of TLRs and Retinoic Acid-Inducible Gene I
J. Immunol.,
December 1, 2006;
177(11):
8008 - 8016.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Dolganiuc, S. Chang, K. Kodys, P. Mandrekar, G. Bakis, M. Cormier, and G. Szabo
Hepatitis C Virus (HCV) Core Protein-Induced, Monocyte-Mediated Mechanisms of Reduced IFN-{alpha} and Plasmacytoid Dendritic Cell Loss in Chronic HCV Infection
J. Immunol.,
November 15, 2006;
177(10):
6758 - 6768.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. W. Boehme, M. Guerrero, and T. Compton
Human Cytomegalovirus Envelope Glycoproteins B and H Are Necessary for TLR2 Activation in Permissive Cells
J. Immunol.,
November 15, 2006;
177(10):
7094 - 7102.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Sato, M. M. Linehan, and A. Iwasaki
Dual recognition of herpes simplex viruses by TLR2 and TLR9 in dendritic cells
PNAS,
November 14, 2006;
103(46):
17343 - 17348.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. S. Patole, R. D. Pawar, M. Lech, D. Zecher, H. Schmidt, S. Segerer, A. Ellwart, A. Henger, M. Kretzler, and H.-J. Anders
Expression and regulation of Toll-like receptors in lupus-like immune complex glomerulonephritis of MRL-Fas(lpr) mice
Nephrol. Dial. Transplant.,
November 1, 2006;
21(11):
3062 - 3073.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. S. Rosenthal and D. H. Zimmerman
Vaccines: all things considered.
Clin. Vaccine Immunol.,
August 1, 2006;
13(8):
821 - 829.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Hayashi, L. C. Hooper, M. S. Chin, C. N. Nagineni, B. Detrick, and J. J. Hooks
Herpes simplex virus 1 (HSV-1) DNA and immune complex (HSV-1-human IgG) elicit vigorous interleukin 6 release from infected corneal cells via Toll-like receptors.
J. Gen. Virol.,
August 1, 2006;
87(Pt 8):
2161 - 2169.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Feldmann, H. D. Nischalke, J. Nattermann, B. Banas, T. Berg, C. Teschendorf, W. Schmiegel, U. Duhrsen, J. Halangk, A. Iwan, et al.
Induction of Interleukin-6 by Hepatitis C Virus Core Protein in Hepatitis C-Associated Mixed Cryoglobulinemia and B-Cell Non-Hodgkin's Lymphoma
Clin. Cancer Res.,
August 1, 2006;
12(15):
4491 - 4498.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S. Hidmark, E. K. L. Nordstrom, P. Dosenovic, M. N. E. Forsell, P. Liljestrom, and G. B. Karlsson Hedestam
Humoral Responses against Coimmunized Protein Antigen but Not against Alphavirus-Encoded Antigens Require Alpha/Beta Interferon Signaling
J. Virol.,
July 15, 2006;
80(14):
7100 - 7110.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Szomolanyi-Tsuda, X. Liang, R. M. Welsh, E. A. Kurt-Jones, and R. W. Finberg
Role for TLR2 in NK Cell-Mediated Control of Murine Cytomegalovirus In Vivo
J. Virol.,
May 1, 2006;
80(9):
4286 - 4291.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Melchjorsen, J. Siren, I. Julkunen, S. R. Paludan, and S. Matikainen
Induction of cytokine expression by herpes simplex virus in human monocyte-derived macrophages and dendritic cells is dependent on virus replication and is counteracted by ICP27 targeting NF-{kappa}B and IRF-3.
J. Gen. Virol.,
May 1, 2006;
87(Pt 5):
1099 - 1108.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. B. Lopez, J. S. Yount, and T. M. Moran
Toll-like receptor-independent triggering of dendritic cell maturation by viruses.
J. Virol.,
April 1, 2006;
80(7):
3128 - 3134.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Matikainen, J. Siren, J. Tissari, V. Veckman, J. Pirhonen, M. Severa, Q. Sun, R. Lin, S. Meri, G. Uze, et al.
Tumor Necrosis Factor Alpha Enhances Influenza A Virus-Induced Expression of Antiviral Cytokines by Activating RIG-I Gene Expression.
J. Virol.,
April 1, 2006;
80(7):
3515 - 3522.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. M. Koelle, J. Huang, M. T. Hensel, and C. L. McClurkan
Innate Immune Responses to Herpes Simplex Virus Type 2 Influence Skin Homing Molecule Expression by Memory CD4+ Lymphocytes
J. Virol.,
March 15, 2006;
80(6):
2863 - 2872.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Guo, S. Garg, K. M. Hill, L. Jayashankar, M. R. Mooney, M. Hoelscher, J. M. Katz, J. M. Boss, and S. Sambhara
A Distal Regulatory Region Is Required for Constitutive and IFN-{beta}-Induced Expression of Murine TLR9 Gene
J. Immunol.,
December 1, 2005;
175(11):
7407 - 7418.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Delale, A. Paquin, C. Asselin-Paturel, M. Dalod, G. Brizard, E. E. M. Bates, P. Kastner, S. Chan, S. Akira, A. Vicari, et al.
MyD88-Dependent and -Independent Murine Cytomegalovirus Sensing for IFN-{alpha} Release and Initiation of Immune Responses In Vivo
J. Immunol.,
November 15, 2005;
175(10):
6723 - 6732.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. E. Hensley, W. Giles-Davis, K. C. McCoy, W. Weninger, and H. C. J. Ertl
Dendritic Cell Maturation, but Not CD8+ T Cell Induction, Is Dependent on Type I IFN Signaling during Vaccination with Adenovirus Vectors
J. Immunol.,
November 1, 2005;
175(9):
6032 - 6041.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Honda, H. Yanai, A. Takaoka, and T. Taniguchi
Regulation of the type I IFN induction: a current view
Int. Immunol.,
November 1, 2005;
17(11):
1367 - 1378.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Wang, E. A. Kurt-Jones, O. S. Shin, M. D. Manchak, M. J. Levin, and R. W. Finberg
Varicella-Zoster Virus Activates Inflammatory Cytokines in Human Monocytes and Macrophages via Toll-Like Receptor 2
J. Virol.,
October 15, 2005;
79(20):
12658 - 12666.
[Abstract]
[Full Text]
[PDF]
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|
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|
|
S. Rothenfusser, N. Goutagny, G. DiPerna, M. Gong, B. G. Monks, A. Schoenemeyer, M. Yamamoto, S. Akira, and K. A. Fitzgerald
The RNA Helicase Lgp2 Inhibits TLR-Independent Sensing of Viral Replication by Retinoic Acid-Inducible Gene-I
J. Immunol.,
October 15, 2005;
175(8):
5260 - 5268.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. N. Aravalli, S. Hu, T. N. Rowen, J. M. Palmquist, and J. R. Lokensgard
Cutting Edge: TLR2-Mediated Proinflammatory Cytokine and Chemokine Production by Microglial Cells in Response to Herpes Simplex Virus
J. Immunol.,
October 1, 2005;
175(7):
4189 - 4193.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Maloney, M. Schroder, and A. G. Bowie
Vaccinia Virus Protein A52R Activates p38 Mitogen-activated Protein Kinase and Potentiates Lipopolysaccharide-induced Interleukin-10
J. Biol. Chem.,
September 2, 2005;
280(35):
30838 - 30844.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Orinska, E. Bulanova, V. Budagian, M. Metz, M. Maurer, and S. Bulfone-Paus
TLR3-induced activation of mast cells modulates CD8+ T-cell recruitment
Blood,
August 1, 2005;
106(3):
978 - 987.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K.-K. Conzelmann
Transcriptional Activation of Alpha/Beta Interferon Genes: Interference by Nonsegmented Negative-Strand RNA Viruses
J. Virol.,
May 1, 2005;
79(9):
5241 - 5248.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Schlender, V. Hornung, S. Finke, M. Gunthner-Biller, S. Marozin, K. Brzozka, S. Moghim, S. Endres, G. Hartmann, and K.-K. Conzelmann
Inhibition of Toll-Like Receptor 7- and 9-Mediated Alpha/Beta Interferon Production in Human Plasmacytoid Dendritic Cells by Respiratory Syncytial Virus and Measles Virus
J. Virol.,
May 1, 2005;
79(9):
5507 - 5515.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. S. Mansur, E. G. Kroon, M. L. Nogueira, R. M.E. Arantes, S. C.O. Rodrigues, S. Akira, R. T. Gazzinelli, and M. A. Campos
Lethal Encephalitis in Myeloid Differentiation Factor 88-Deficient Mice Infected with Herpes Simplex Virus 1
Am. J. Pathol.,
May 1, 2005;
166(5):
1419 - 1426.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Schoenemeyer, B. J. Barnes, Margo. E. Mancl, E. Latz, N. Goutagny, P. M. Pitha, K. A. Fitzgerald, and D. T. Golenbock
The Interferon Regulatory Factor, IRF5, Is a Central Mediator of Toll-like Receptor 7 Signaling
J. Biol. Chem.,
April 29, 2005;
280(17):
17005 - 17012.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. B. Bekeredjian-Ding, M. Wagner, V. Hornung, T. Giese, M. Schnurr, S. Endres, and G. Hartmann
Plasmacytoid Dendritic Cells Control TLR7 Sensitivity of Naive B Cells via Type I IFN
J. Immunol.,
April 1, 2005;
174(7):
4043 - 4050.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Kamogawa-Schifter, J. Ohkawa, S. Namiki, N. Arai, K.-i. Arai, and Y. Liu
Ly49Q defines 2 pDC subsets in mice
Blood,
April 1, 2005;
105(7):
2787 - 2792.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Uematsu, S. Sato, M. Yamamoto, T. Hirotani, H. Kato, F. Takeshita, M. Matsuda, C. Coban, K. J. Ishii, T. Kawai, et al.
Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-{alpha} induction
J. Exp. Med.,
March 21, 2005;
201(6):
915 - 923.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Stack, I. R. Haga, M. Schroder, N. W. Bartlett, G. Maloney, P. C. Reading, K. A. Fitzgerald, G. L. Smith, and A. G. Bowie
Vaccinia virus protein A46R targets multiple Toll-like-interleukin-1 receptor adaptors and contributes to virulence
J. Exp. Med.,
March 21, 2005;
201(6):
1007 - 1018.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Abe, H. Hemmi, H. Miyamoto, K. Moriishi, S. Tamura, H. Takaku, S. Akira, and Y. Matsuura
Involvement of the Toll-Like Receptor 9 Signaling Pathway in the Induction of Innate Immunity by Baculovirus
J. Virol.,
March 1, 2005;
79(5):
2847 - 2858.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Siren, J. Pirhonen, I. Julkunen, and S. Matikainen
IFN-{alpha} Regulates TLR-Dependent Gene Expression of IFN-{alpha}, IFN-{beta}, IL-28, and IL-29
J. Immunol.,
February 15, 2005;
174(4):
1932 - 1937.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Jahrsdorfer, L. Muhlenhoff, S. E. Blackwell, M. Wagner, H. Poeck, E. Hartmann, R. Jox, T. Giese, B. Emmerich, S. Endres, et al.
B-Cell Lymphomas Differ in their Responsiveness to CpG Oligodeoxynucleotides
Clin. Cancer Res.,
February 15, 2005;
11(4):
1490 - 1499.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. McKenna, A.-S. Beignon, and N. Bhardwaj
Plasmacytoid Dendritic Cells: Linking Innate and Adaptive Immunity
J. Virol.,
January 1, 2005;
79(1):
17 - 27.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Q. Khan, Q. Chen, Z.-Q. Wu, J. C. Paton, and C. M. Snapper
Both Innate Immunity and Type 1 Humoral Immunity to Streptococcus pneumoniae Are Mediated by MyD88 but Differ in Their Relative Levels of Dependence on Toll-Like Receptor 2
Infect. Immun.,
January 1, 2005;
73(1):
298 - 307.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Takeda and S. Akira
Toll-like receptors in innate immunity
Int. Immunol.,
January 1, 2005;
17(1):
1 - 14.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Gregory, D. Hargett, D. Holmes, E. Money, and S. L. Bachenheimer
Efficient Replication by Herpes Simplex Virus Type 1 Involves Activation of the I{kappa}B Kinase-I{kappa}B-p65 Pathway
J. Virol.,
December 15, 2004;
78(24):
13582 - 13590.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Stockinger, B. Reutterer, B. Schaljo, C. Schellack, S. Brunner, T. Materna, M. Yamamoto, S. Akira, T. Taniguchi, P. J. Murray, et al.
IFN Regulatory Factor 3-Dependent Induction of Type I IFNs by Intracellular Bacteria Is Mediated by a TLR- and Nod2-Independent Mechanism
J. Immunol.,
December 15, 2004;
173(12):
7416 - 7425.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. B. Lopez, B. Moltedo, L. Alexopoulou, L. Bonifaz, R. A. Flavell, and T. M. Moran
TLR-Independent Induction of Dendritic Cell Maturation and Adaptive Immunity by Negative-Strand RNA Viruses
J. Immunol.,
December 1, 2004;
173(11):
6882 - 6889.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Sato and A. Iwasaki
From The Cover: Induction of antiviral immunity requires Toll-like receptor signaling in both stromal and dendritic cell compartments
PNAS,
November 16, 2004;
101(46):
16274 - 16279.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Hornung, J. Schlender, M. Guenthner-Biller, S. Rothenfusser, S. Endres, K.-K. Conzelmann, and G. Hartmann
Replication-Dependent Potent IFN-{alpha} Induction in Human Plasmacytoid Dendritic Cells by a Single-Stranded RNA Virus
J. Immunol.,
November 15, 2004;
173(10):
5935 - 5943.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Zhang, S. C. Das, C. Kotalik, A. K. Pattnaik, and L. Zhang
The Latent Membrane Protein 1 of Epstein-Barr Virus Establishes an Antiviral State via Induction of Interferon-stimulated Genes
J. Biol. Chem.,
October 29, 2004;
279(44):
46335 - 46342.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Honda, H. Yanai, T. Mizutani, H. Negishi, N. Shimada, N. Suzuki, Y. Ohba, A. Takaoka, W.-C. Yeh, and T. Taniguchi
Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling
PNAS,
October 26, 2004;
101(43):
15416 - 15421.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. Barnes, J. Richards, M. Mancl, S. Hanash, L. Beretta, and P. M. Pitha
Global and Distinct Targets of IRF-5 and IRF-7 during Innate Response to Viral Infection
J. Biol. Chem.,
October 22, 2004;
279(43):
45194 - 45207.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Schlecht, S. Garcia, N. Escriou, A. A. Freitas, C. Leclerc, and G. Dadaglio
Murine plasmacytoid dendritic cells induce effector/memory CD8+ T-cell responses in vivo after viral stimulation
Blood,
September 15, 2004;
104(6):
1808 - 1815.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. T. Melroe, N. A. DeLuca, and D. M. Knipe
Herpes Simplex Virus 1 Has Multiple Mechanisms for Blocking Virus-Induced Interferon Production
J. Virol.,
August 15, 2004;
78(16):
8411 - 8420.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Whitmore, M. J. DeVeer, A. Edling, R. K. Oates, B. Simons, D. Lindner, and B. R. G. Williams
Synergistic Activation of Innate Immunity by Double-Stranded RNA and CpG DNA Promotes Enhanced Antitumor Activity
Cancer Res.,
August 15, 2004;
64(16):
5850 - 5860.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Hochrein, B. Schlatter, M. O'Keeffe, C. Wagner, F. Schmitz, M. Schiemann, S. Bauer, M. Suter, and H. Wagner
Herpes simplex virus type-1 induces IFN-{alpha} production via Toll-like receptor 9-dependent and -independent pathways
PNAS,
August 3, 2004;
101(31):
11416 - 11421.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Granelli-Piperno, A. Golebiowska, C. Trumpfheller, F. P. Siegal, and R. M. Steinman
HIV-1-infected monocyte-derived dendritic cells do not undergo maturation but can elicit IL-10 production and T cell regulation
PNAS,
May 18, 2004;
101(20):
7669 - 7674.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Lund, L. Alexopoulou, A. Sato, M. Karow, N. C. Adams, N. W. Gale, A. Iwasaki, and R. A. Flavell
Recognition of single-stranded RNA viruses by Toll-like receptor 7
PNAS,
April 13, 2004;
101(15):
5598 - 5603.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. S. Diebold, T. Kaisho, H. Hemmi, S. Akira, and C. Reis e Sousa
Innate Antiviral Responses by Means of TLR7-Mediated Recognition of Single-Stranded RNA
Science,
March 5, 2004;
303(5663):
1529 - 1531.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
Top
Abstract
Introduction
) and MyD88–/–
(
)
mice and cultured for 36 hours (2 x 106 cells/mL) with KOS HSV-1 at the indicated MOI or 3 µg/mL CpG ODN 2216. (B) IPC (top row), CD11b+ DCs (middle row), and CD11b– DC (bottom row) were sorted from wild-type and MyD88–/– CD11c+ splenocytes and were cultured with 2 MOI HSV-1 or 3 µg/mL CpG ODN 2216 for 36 hours (5 x 104 cells/150 µL/well). (C) Bone marrow–derived wild-type and MyD88–/– IPCs were incubated with HSV-1 (0.04-5 MOI) or CpG ODN 2216 (3 µg/mL) for 36 hours at 106 cells/mL. IFN-
