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RIG-I-like receptor activation by dengue virus drives follicular T helper cell formation and antibody production.

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  • معلومة اضافية
    • Author-Supplied Keywords:
      Animal cells
      Antibodies
      Antibody-producing cells
      B cells
      Biochemistry
      Biology and life sciences
      Blood cells
      Cell biology
      Cell differentiation
      Cellular types
      Cytophotometry
      Developmental biology
      Enzyme-linked immunoassays
      Flow cytometry
      Gene expression
      Gene regulation
      Genetics
      Immune cells
      Immune physiology
      Immune system proteins
      Immunoassays
      Immunologic techniques
      Immunology
      Medicine and health sciences
      Microbiology
      Non-coding RNA
      Nucleic acids
      Physiology
      Proteins
      Research and analysis methods
      Research Article
      RNA
      Small interfering RNAs
      Spectrophotometry
      Spectrum analysis techniques
      T cells
      Viral replication
      Virology
      White blood cells
    • Abstract:
      Follicular T helper cells (TFH) are fundamental in orchestrating effective antibody-mediated responses critical for immunity against viral infections and effective vaccines. However, it is unclear how virus infection leads to TFH induction. We here show that dengue virus (DENV) infection of human dendritic cells (DCs) drives TFH formation via crosstalk of RIG-I-like receptor (RLR) RIG-I and MDA5 with type I Interferon (IFN) signaling. DENV infection leads to RLR-dependent IKKε activation, which phosphorylates IFNα/β receptor-induced STAT1 to drive IL-27 production via the transcriptional complex ISGF3. Inhibiting RLR activation as well as neutralizing antibodies against IL-27 prevented TFH formation. DENV-induced CXCR5+PD-1+Bcl-6+ TFH cells secreted IL-21 and activated B cells to produce IgM and IgG. Notably, RLR activation by synthetic ligands also induced IL-27 secretion and TFH polarization. These results identify an innate mechanism by which antibodies develop during viral disease and identify RLR ligands as potent adjuvants for TFH-promoting vaccination strategies. [ABSTRACT FROM AUTHOR]
    • Abstract:
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    • Author Affiliations:
      1Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
      2Amsterdam Infection & Immunity Institute, Amsterdam, the Netherlands
    • ISSN:
      1553-7366
    • Accession Number:
      10.1371/journal.ppat.1006738
    • Accession Number:
      126463864
  • Citations
    • ABNT:
      SPROKHOLT, J. K. et al. RIG-I-like receptor activation by dengue virus drives follicular T helper cell formation and antibody production. PLoS Pathogens, [s. l.], v. 13, n. 11, p. 1–19, 2017. DOI 10.1371/journal.ppat.1006738. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=asn&AN=126463864&custid=s8280428. Acesso em: 15 ago. 2020.
    • AMA:
      Sprokholt JK, Kaptein TM, van Hamme JL, Overmars RJ, Gringhuis SI, Geijtenbeek TBH. RIG-I-like receptor activation by dengue virus drives follicular T helper cell formation and antibody production. PLoS Pathogens. 2017;13(11):1-19. doi:10.1371/journal.ppat.1006738
    • APA:
      Sprokholt, J. K., Kaptein, T. M., van Hamme, J. L., Overmars, R. J., Gringhuis, S. I., & Geijtenbeek, T. B. H. (2017). RIG-I-like receptor activation by dengue virus drives follicular T helper cell formation and antibody production. PLoS Pathogens, 13(11), 1–19. https://doi.org/10.1371/journal.ppat.1006738
    • Chicago/Turabian: Author-Date:
      Sprokholt, Joris K., Tanja M. Kaptein, John L. van Hamme, Ronald J. Overmars, Sonja I. Gringhuis, and Teunis B. H. Geijtenbeek. 2017. “RIG-I-like Receptor Activation by Dengue Virus Drives Follicular T Helper Cell Formation and Antibody Production.” PLoS Pathogens 13 (11): 1–19. doi:10.1371/journal.ppat.1006738.
    • Harvard:
      Sprokholt, J. K. et al. (2017) ‘RIG-I-like receptor activation by dengue virus drives follicular T helper cell formation and antibody production’, PLoS Pathogens, 13(11), pp. 1–19. doi: 10.1371/journal.ppat.1006738.
    • Harvard: Australian:
      Sprokholt, JK, Kaptein, TM, van Hamme, JL, Overmars, RJ, Gringhuis, SI & Geijtenbeek, TBH 2017, ‘RIG-I-like receptor activation by dengue virus drives follicular T helper cell formation and antibody production’, PLoS Pathogens, vol. 13, no. 11, pp. 1–19, viewed 15 August 2020, .
    • MLA:
      Sprokholt, Joris K., et al. “RIG-I-like Receptor Activation by Dengue Virus Drives Follicular T Helper Cell Formation and Antibody Production.” PLoS Pathogens, vol. 13, no. 11, Nov. 2017, pp. 1–19. EBSCOhost, doi:10.1371/journal.ppat.1006738.
    • Chicago/Turabian: Humanities:
      Sprokholt, Joris K., Tanja M. Kaptein, John L. van Hamme, Ronald J. Overmars, Sonja I. Gringhuis, and Teunis B. H. Geijtenbeek. “RIG-I-like Receptor Activation by Dengue Virus Drives Follicular T Helper Cell Formation and Antibody Production.” PLoS Pathogens 13, no. 11 (November 29, 2017): 1–19. doi:10.1371/journal.ppat.1006738.
    • Vancouver/ICMJE:
      Sprokholt JK, Kaptein TM, van Hamme JL, Overmars RJ, Gringhuis SI, Geijtenbeek TBH. RIG-I-like receptor activation by dengue virus drives follicular T helper cell formation and antibody production. PLoS Pathogens [Internet]. 2017 Nov 29 [cited 2020 Aug 15];13(11):1–19. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=asn&AN=126463864&custid=s8280428