Sequential Activation of Two Pathogen-Sensing Pathways Required for Type I Interferon Expression and Resistance to an Acute DNA Virus Infection
| Autor: | Eric B. Wong, Savita Nair, Reto A. Schwendener, Ren-Huan Xu, Luis J. Sigal, Shinu John, Xueying Ma, Sanda Remakus, Daniel Rubio, Mark J. Shlomchik, Felicia Roscoe |
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| Přispěvatelé: | University of Zurich, Sigal, Luis J |
| Rok vydání: | 2015 |
| Předmět: |
Ectromelia virus
Interferon Regulatory Factor-7 Immunology 610 Medicine & health Monocytes Article Proinflammatory cytokine 03 medical and health sciences Mice 0302 clinical medicine Interferon medicine Immunology and Allergy Animals Ectromelia Infectious 030304 developmental biology Mice Knockout 2403 Immunology 0303 health sciences biology Reverse Transcriptase Polymerase Chain Reaction 10061 Institute of Molecular Cancer Research TLR9 Membrane Proteins DNA virus 2725 Infectious Diseases biology.organism_classification Flow Cytometry Virology DNA Virus Infections Mice Mutant Strains 3. Good health Cell biology Infectious Diseases Toll-Like Receptor 9 Interferon Type I Myeloid Differentiation Factor 88 2723 Immunology and Allergy 570 Life sciences IRF7 Lymph Nodes Interferon type I 030215 immunology medicine.drug Interferon regulatory factors Signal Transduction |
| Zdroj: | Immunity. 43(6) |
| ISSN: | 1097-4180 |
| Popis: | SummaryToll-like receptor 9 (TLR9), its adaptor MyD88, the downstream transcription factor interferon regulatory factor 7 (IRF7), and type I interferons (IFN-I) are all required for resistance to infection with ectromelia virus (ECTV). However, it is not known how or in which cells these effectors function to promote survival. Here, we showed that after infection with ECTV, the TLR9-MyD88-IRF7 pathway was necessary in CD11c+ cells for the expression of proinflammatory cytokines and the recruitment of inflammatory monocytes (iMos) to the draining lymph node (dLN). In the dLN, the major producers of IFN-I were infected iMos, which used the DNA sensor-adaptor STING to activate IRF7 and nuclear factor κB (NF-κB) signaling to induce the expression of IFN-α and IFN-β, respectively. Thus, in vivo, two pathways of DNA pathogen sensing act sequentially in two distinct cell types to orchestrate resistance to a viral disease. |
| Databáze: | OpenAIRE |
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