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Journal of General Virology header logo Journal of General Virology

Volume 97, Issue 7

Altered immune response of immature dendritic cells following dengue virus infection in the presence of specific antibodies No Access

Abstract

Dengue virus (DENV) replication is known to prevent maturation of infected dendritic cells (DCs) thereby impeding the development of adequate immunity. During secondary DENV infection, dengue-specific antibodies can suppress DENV replication in immature DCs (immDCs), however how dengue-antibody complexes (DENV-IC) influence the phenotype of DCs remains elusive. Here, we evaluated the maturation state and cytokine profile of immDCs exposed to DENV-ICs. Indeed, DENV infection of immDCs in the absence of antibodies was hallmarked by blunted upregulation of CD83, CD86 and the major histocompatibility complex molecule HLA-DR. In contrast, DENV infection in the presence of neutralizing antibodies triggered full DC maturation and induced a balanced inflammatory cytokine response. Moreover, DENV infection under non-neutralizing conditions prompted upregulation of CD83 and CD86 but not HLA-DR, and triggered production of pro-inflammatory cytokines. The effect of DENV-IC was found to be dependent on the engagement of FcγRIIa. Altogether, our data show that the presence of DENV-IC alters the phenotype and cytokine profile of DCs.

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Keyword(s): DC maturation , dendritic cells , dengue virus , dengue-immune sera , FcY receptor and neutralization
© 2016 The Authors
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/content/journal/jgv/10.1099/jgv.0.000491
2016-07-01
2025-03-19
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References

  1. Banchereau J., Steinman R. M. 1998; Dendritic cells and the control of immunity. Nature 392:245–252 [View Article][PubMed]
     [Google Scholar]
  2. Bhatt S., Gething P. W., Brady O. J., Messina J. P., Farlow A. W., Moyes C. L., Drake J. M., Brownstein J. S., Hoen A. G. et al. 2013; The global distribution and burden of dengue. Nature 496:504–507 [View Article][PubMed]
     [Google Scholar]
  3. Boonnak K., Dambach K. M., Donofrio G. C., Tassaneetrithep B., Marovich M. A. 2011; Cell type specificity and host genetic polymorphisms influence antibody-dependent enhancement of dengue virus infection. J Virol 85:1671–1683 [View Article][PubMed]
     [Google Scholar]
  4. Boonnak K., Slike B. M., Burgess T. H., Mason R. M., Wu S. J., Sun P., Porter K., Rudiman I. F., Yuwono D. et al. 2008; Role of dendritic cells in antibody-dependent enhancement of dengue virus infection. J Virol 82:3939–3951 [View Article][PubMed]
     [Google Scholar]
  5. Cella M., Sallusto F., Lanzavecchia A. 1997; Origin, maturation and antigen presenting function of dendritic cells. Curr Opin Immunol 9:10–16[PubMed] [CrossRef]
     [Google Scholar]
  6. Chang T. H., Chen S. R., Yu C. Y., Lin Y. S., Chen Y. S., Kubota T., Lin Y. L. 2012; Dengue virus serotype 2 blocks extracellular signal-regulated kinase and nuclear factor-kappaB activation to downregulate cytokine production. PloS One 7:e41635 [CrossRef]
     [Google Scholar]
  7. Chawla T., Chan K. R., Zhang S. L., Tan H. C., Lim A. P., Hanson B. J., Ooi E. E. 2013; Dengue virus neutralization in cells expressing Fc gamma receptors. PLoS One 8:e65231 [View Article][PubMed]
     [Google Scholar]
  8. Costa V. V., Fagundes C. T., Souza D. G., Teixeira M. M. 2013; Inflammatory and innate immune responses in dengue infection: protection versus disease induction. Am J Pathol 182:1950–1961 [View Article][PubMed]
     [Google Scholar]
  9. de Alwis R., Beltramello M., Messer W. B., Sukupolvi-Petty S., Wahala W. M., Kraus A., Olivarez N. P., Pham Q., Brien J. D. et al. 2011; In-depth analysis of the antibody response of individuals exposed to primary dengue virus infection. PLoS Negl Trop Dis 5:e1188 [View Article][PubMed]
     [Google Scholar]
  10. de Witte L., Abt M., Schneider-Schaulies S., van Kooyk Y., Geijtenbeek T. B. 2006; Measles virus targets DC-SIGN to enhance dendritic cell infection. J Virol 80:3477–3486 [View Article][PubMed]
     [Google Scholar]
  11. Dejnirattisai W., Webb A. I., Chan V., Jumnainsong A., Davidson A., Mongkolsapaya J., Screaton G. 2011; Lectin switching during dengue virus infection. J Infect Dis 203:1775–1783 [View Article][PubMed]
     [Google Scholar]
  12. den Dunnen J., Vogelpoel L. T., Wypych T., Muller F. J., de Boer L., Kuijpers T. W., Zaat S. A., Kapsenberg M. L., de Jong E. C. 2012; IgG opsonization of bacteria promotes Th17 responses via synergy between TLRs and FcγRIIa in human dendritic cells. Blood 120:112–121 [View Article][PubMed]
     [Google Scholar]
  13. Dudek A. M., Martin S., Garg A. D., Agostinis P. 2013; Immature, semi-mature, and fully mature dendritic cells: toward a DC-cancer cells interface that augments anticancer immunity. Front Immunol 4:438 [View Article][PubMed]
     [Google Scholar]
  14. Endy T. P., Nisalak A., Chunsuttitwat S., Vaughn D. W., Green S., Ennis F. A., Rothman A. L., Libraty D. H. 2004; Relationship of preexisting dengue virus (DV) neutralizing antibody levels to viremia and severity of disease in a prospective cohort study of DV infection in Thailand. J Infect Dis 189:990–1000 [View Article][PubMed]
     [Google Scholar]
  15. Green S., Rothman A. 2006; Immunopathological mechanisms in dengue and dengue hemorrhagic fever. Curr Opin Infect Dis 19:429–436 [View Article][PubMed]
     [Google Scholar]
  16. Gudmundsson G., Bosch A., Davidson B. L., Berg D. J., Hunninghake G. W. 1998; Interleukin-10 modulates the severity of hypersensitivity pneumonitis in mice. Am J Respir Cell Mol Biol 19:812–818 [View Article][PubMed]
     [Google Scholar]
  17. Halstead S. B. 2003; Neutralization and antibody-dependent enhancement of dengue viruses. Adv Virus Res 60:421–467[PubMed] [CrossRef]
     [Google Scholar]
  18. Halstead S. B. 2007; Dengue. Lancet 370:1644–1652 [View Article][PubMed]
     [Google Scholar]
  19. Hause A. M., Perez-Padilla J., Horiuchi K., Han G. S., Hunsperger E., Aiwazian J., Margolis H. S., Tomashek K. M. 2015; Epidemiology of dengue among children aged < 18 months-Puerto Rico, 1999–2011. Am J Trop Med Hyg 94:404–408 [View Article][PubMed]
     [Google Scholar]
  20. Ho L. J., Wang J. J., Shaio M. F., Kao C. L., Chang D. M., Han S. W., Lai J. H. 2001; Infection of human dendritic cells by dengue virus causes cell maturation and cytokine production. J Immunol 166:1499–1506[PubMed] [CrossRef]
     [Google Scholar]
  21. Kliks S. C., Nimmanitya S., Nisalak A., Burke D. S. 1988; Evidence that maternal dengue antibodies are important in the development of dengue hemorrhagic fever in infants. Am J Trop Med Hyg 38:411–419[PubMed]
     [Google Scholar]
  22. Libraty D. H., Pichyangkul S., Ajariyakhajorn C., Endy T. P., Ennis F. A. 2001; Human dendritic cells are activated by dengue virus infection: enhancement by gamma interferon and implications for disease pathogenesis. J Virol 75:3501–3508 [View Article][PubMed]
     [Google Scholar]
  23. Lilley B. N., Ploegh H. L. 2005; Viral modulation of antigen presentation: manipulation of cellular targets in the ER and beyond. Immunol Rev 207:126–144 [View Article][PubMed]
     [Google Scholar]
  24. Liu L., Chavan R., Feinberg M. B. 2008; Dendritic cells are preferentially targeted among hematolymphocytes by modified vaccinia virus ankara and play a key role in the induction of virus-specific T cell responses in vivo . BMC Immunology 9:15 [View Article][PubMed]
     [Google Scholar]
  25. Lutz M. B., Schuler G. 2002; Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity?. Trends Immunol 23:445–449 [View Article][PubMed]
     [Google Scholar]
  26. Mangada M. M., Rothman A. L. 2005; Altered cytokine responses of dengue-specific CD4+ T cells to heterologous serotypes. J Immunol 175:2676–2683[PubMed] [CrossRef]
     [Google Scholar]
  27. Marovich M., Grouard-Vogel G., Louder M., Eller M., Sun W., Wu S. J., Putvatana R., Murphy G., Tassaneetrithep B. et al. 2001; Human dendritic cells as targets of dengue virus infection. J Investig Dermatol Symp Proc 6:219–224 [View Article][PubMed]
     [Google Scholar]
  28. Mathew A., Kurane I., Green S., Vaughn D. W., Kalayanarooj S., Suntayakorn S., Ennis F. A., Rothman A. L. 1999; Impaired T cell proliferation in acute dengue infection. J Immunol 162:5609–5615
     [Google Scholar]
  29. Miller R. L., Meng T. C., Tomai M. A. 2008; The antiviral activity of Toll-like receptor 7 and 7/8 agonists. Drug News Perspect 21:69–87 [View Article][PubMed]
     [Google Scholar]
  30. Modhiran N., Kalayanarooj S., Ubol S. 2010; Subversion of innate defenses by the interplay between DENV and pre-existing enhancing antibodies: TLRs signaling collapse. PLoS Negl Trop Dis 4:e924 [View Article][PubMed]
     [Google Scholar]
  31. Moi M. L., Lim C. K., Takasaki T., Kurane I. 2010; Involvement of the Fc gamma receptor IIA cytoplasmic domain in antibody-dependent enhancement of dengue virus infection. J Gen Virol 91:103–111 [View Article][PubMed]
     [Google Scholar]
  32. Muñoz-Jordan J. L., Sánchez-Burgos G. G., Laurent-Rolle M., García-Sastre A. 2003; Inhibition of interferon signaling by dengue virus. Proc Natl Acad Sci U S A 100:14333–14338 [View Article][PubMed]
     [Google Scholar]
  33. Muñoz-Jordán J. L. 2010; Subversion of interferon by dengue virus. Curr Top Microbiol Immunol 338:35–44 [View Article][PubMed]
     [Google Scholar]
  34. Navarro-Sánchez E., Desprès P., Cedillo-Barrón L. 2005; Innate immune responses to dengue virus. Arch Med Res 36:425–435 [View Article][PubMed]
     [Google Scholar]
  35. Nightingale Z. D., Patkar C., Rothman A. L. 2008; Viral replication and paracrine effects result in distinct, functional responses of dendritic cells following infection with dengue 2 virus. J Leukoc Biol 84:1028–1038 [View Article][PubMed]
     [Google Scholar]
  36. Nimmerjahn F., Ravetch J. V. 2008; Fcgamma receptors as regulators of immune responses. Nat Rev Immunol 8:34–47 [View Article][PubMed]
     [Google Scholar]
  37. Oreshkova N., Wichgers Schreur P. J., Spel L., Vloet R. P., Moormann R. J., Boes M., Kortekaas J. 2015; Nonspreading Rift Valley fever virus infection of human dendritic cells results in downregulation of CD83 and full maturation of bystander cells. PLoS One 10:e0142670 [View Article][PubMed]
     [Google Scholar]
  38. Palmer D. R., Sun P., Celluzzi C., Bisbing J., Pang S., Sun W., Marovich M. A., Burgess T. 2005; Differential effects of dengue virus on infected and bystander dendritic cells. J Virol 79:2432–2439 [View Article][PubMed]
     [Google Scholar]
  39. Pang T., Cardosa M. J., Guzman M. G. 2007; Of cascades and perfect storms: the immunopathogenesis of dengue haemorrhagic fever-dengue shock syndrome (DHF/DSS). Immunol Cell Biol 85:43–45 [View Article][PubMed]
     [Google Scholar]
  40. Regnault A., Lankar D., Lacabanne V., Rodriguez A., Théry C., Rescigno M., Saito T., Verbeek S., Bonnerot C. et al. 1999; Fcgamma receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization. J Exp Med 189:371–380[PubMed] [CrossRef]
     [Google Scholar]
  41. Reich N. G., Shrestha S., King A. A., Rohani P., Lessler J., Kalayanarooj S., Yoon I. K., Gibbons R. V., Burke D. S., Cummings D. A. 2013; Interactions between serotypes of dengue highlight epidemiological impact of cross-immunity. J R Soc Interface 10:20130414 [View Article][PubMed]
     [Google Scholar]
  42. Richter M. K. S., da Silva Voorham J. M., Torres Pedraza S., Hoornweg T. E., van de Pol D. P. I., Rodenhuis-Zybert I. A., Wilschut J., Smit J. M. 2014; Immature dengue virus is infectious in human immature dendritic cells via interaction with the receptor molecule DC-SIGN. PLoS ONE 9:e98785 [View Article]
     [Google Scholar]
  43. Rinaldo C. R. 2013; HIV-1 trans infection of CD4(+) T cells by professional antigen presenting cells. Scientifica (Cairo) 2013:164203 [View Article][PubMed]
     [Google Scholar]
  44. Rodenhuis-Zybert I. A., van der Schaar H. M., da Silva Voorham J. M., van der Ende-Metselaar H., Lei H. Y., Wilschut J., Smit J. M. 2010; Immature dengue virus: a veiled pathogen?. PLoS Pathog 6:e1000718 [View Article][PubMed]
     [Google Scholar]
  45. Rodrigo W. W., Jin X., Blackley S. D., Rose R. C., Schlesinger J. J. 2006; Differential enhancement of dengue virus immune complex infectivity mediated by signaling-competent and signaling-incompetent human Fcgamma RIA (CD64) or FcgammaRIIA (CD32). J Virol 80:10128–10138 [View Article][PubMed]
     [Google Scholar]
  46. Rodriguez-Madoz J. R., Belicha-Villanueva A., Bernal-Rubio D., Ashour J., Ayllon J., Fernandez-Sesma A. 2010a; Inhibition of the type I interferon response in human dendritic cells by dengue virus infection requires a catalytically active NS2B3 complex. J Virol 84:9760–9774 [View Article][PubMed]
     [Google Scholar]
  47. Rodriguez-Madoz J. R., Bernal-Rubio D., Kaminski D., Boyd K., Fernandez-Sesma A. 2010b; Dengue virus inhibits the production of type I interferon in primary human dendritic cells. J Virol 84:4845–4850 [View Article][PubMed]
     [Google Scholar]
  48. Rothman A. L. 2011; Immunity to dengue virus: a tale of original antigenic sin and tropical cytokine storms. Nat Rev Immunol 11:532–543 [View Article][PubMed]
     [Google Scholar]
  49. Sanchez V., Hessler C., DeMonfort A., Lang J., Guy B. 2006; Comparison by flow cytometry of immune changes induced in human monocyte-derived dendritic cells upon infection with dengue 2 live-attenuated vaccine or 16681 parental strain. FEMS Immunol Med Microbiol 46:113–123 [View Article][PubMed]
     [Google Scholar]
  50. Schmid M. A., Harris E. 2014; Monocyte recruitment to the dermis and differentiation to dendritic cells increases the targets for dengue virus replication. PLoS Pathog 10:e1004541 [View Article][PubMed]
     [Google Scholar]
  51. Schuurhuis D. H., van Montfoort N., Ioan-Facsinay A., Jiawan R., Camps M., Nouta J., Melief C. J., Verbeek J. S., Ossendorp F. 2006; Immune complex-loaded dendritic cells are superior to soluble immune complexes as antitumor vaccine. J Immunol 176:4573–4580[PubMed] [CrossRef]
     [Google Scholar]
  52. Simmons C. P., Chau T. N., Thuy T. T., Tuan N. M., Hoang D. M., Thien N. T., Lien le B., Quy N. T., Hieu N. T. et al. 2007; Maternal antibody and viral factors in the pathogenesis of dengue virus in infants. J Infect Dis 196:416–424 [View Article][PubMed]
     [Google Scholar]
  53. Soundravally R., Hoti S. L., Patil S. A., Cleetus C. C., Zachariah B., Kadhiravan T., Narayanan P., Kumar B. A. 2014; Association between proinflammatory cytokines and lipid peroxidation in patients with severe dengue disease around defervescence. Int J Infect Dis 18:68–72 [View Article][PubMed]
     [Google Scholar]
  54. Sun P., Fernandez S., Marovich M. A., Palmer D. R., Celluzzi C. M., Boonnak K., Liang Z., Subramanian H., Porter K. R. et al. 2009; Functional characterization of ex vivo blood myeloid and plasmacytoid dendritic cells after infection with dengue virus. Virology 383:207–215 [View Article][PubMed]
     [Google Scholar]
  55. van der Poll T., Marchant A., Buurman W. A., Berman L., Keogh C. V., Lazarus D. D., Nguyen L., Goldman M., Moldawer L. L., Lowry S. F. 1995; Endogenous IL-10 protects mice from death during septic peritonitis. J Immunol 155:5397–5401[PubMed]
     [Google Scholar]
  56. van der Schaar H. M., Rust M. J., Chen C., van der Ende-Metselaar H., Wilschut J., Zhuang X., Smit J. M. 2008; Dissecting the cell entry pathway of dengue virus by single-particle tracking in living cells. PLoS Pathog 4:e1000244 [View Article][PubMed]
     [Google Scholar]
  57. van der Schaar H. M., Rust M. J., Waarts B. L., van der Ende-Metselaar H., Kuhn R. J., Wilschut J., Zhuang X., Smit J. M. 2007; Characterization of the early events in dengue virus cell entry by biochemical assays and single-virus tracking. J Virol 81:12019–12028 [View Article][PubMed]
     [Google Scholar]
  58. van der Schaar H. M., Wilschut J. C., Smit J. M. 2009; Role of antibodies in controlling dengue virus infection. Immunobiology 214:613–629 [View Article][PubMed]
     [Google Scholar]
  59. Vogelpoel L. T., Hansen I. S., Rispens T., Muller F. J., van Capel T. M., Turina M. C., Vos J. B., Baeten D. L., Kapsenberg M. L. et al. 2014; Fc gamma receptor-TLR cross-talk elicits pro-inflammatory cytokine production by human M2 macrophages. Nat Commun 5:5444 [View Article][PubMed]
     [Google Scholar]
  60. WHO 1997Dengue hemorrhagic fever: diagnosis, treatment, prevention and control world health organization;
     [Google Scholar]
  61. Wu S. J., Grouard-Vogel G., Sun W., Mascola J. R., Brachtel E., Putvatana R., Louder M. K., Filgueira L., Marovich M. A. et al. 2000; Human skin Langerhans cells are targets of dengue virus infection. Nat Med 6:816–820 [View Article][PubMed]
     [Google Scholar]
  62. Yao Y., Li W., Kaplan M. H., Chang C. H. 2005; Interleukin (IL)-4 inhibits IL-10 to promote IL-12 production by dendritic cells. J Exp Med 201:1899–1903 [View Article][PubMed]
     [Google Scholar]
  63. Zybert I. A., van der Ende-Metselaar H., Wilschut J., Smit J. M. 2008; Functional importance of dengue virus maturation: infectious properties of immature virions. J Gen Virol 89:3047–3051 [View Article][PubMed]
     [Google Scholar]
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Altered immune response of immature dendritic cells following dengue virus infection in the presence of specific antibodies
J. Gen. Virol. 97, 1584 (2016); https://doi.org/10.1099/jgv.0.000491
/content/journal/jgv/10.1099/jgv.0.000491
/content/journal/jgv/10.1099/jgv.0.000491
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