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Decreased Peripheral Dendritic Cell Numbers in Dengue Virus Infection

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Abstract

Laboratory predictors of severe forms of dengue virus (DENV) infection are needed. These clinical forms seem to be associated with high viremia, stressing the importance of immune responses, which could involve dendritic cells (DC). Yet, very few studies have evaluated DC after DENV infection. We assessed peripheral blood DC subset numbers in mild and severe forms of dengue in 44 patients, older than 15 years old, infected with serotypes DENV-2, 3 or 4. Patients were divided in high, intermediate and no detectable viremia according to results of molecular biology amplification of DENV. Serological status of anti-DENV IgG or IgM determined primary or secondary infections. Plasmacytoid and myeloid DC absolute and relative numbers were reduced in infected patients when compared to an age-matched healthy control group, but no significant differences in DC numbers were observed between mild or severe forms of disease. A severe disease was more frequent in patients infected with DENV-2 serotype and with secondary infection but no significant differences in DC subset numbers were found related to these variables. Viremia levels did not correlate to disease severity yet were associated to lower DC numbers. Plasmacytoid DC numbers were significantly lower in high and intermediate viremia groups compared to non-infected controls, but not in no detectable viremia patients. Myeloid DC numbers were also significantly lower than controls, even in no detectable viremia patients. These results confirm that circulating DC subset numbers are reduced after DENV infection, although this is not a biomarker of severe forms of dengue in adults.

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References

  1. Weaver SC, Vasilakis N. Molecular evolution of dengue viruses: contributions of phylogenetics to understanding the history and epidemiology of the preeminent arboviral disease. Infect Genet Evol. 2009;9:523–40.

    Article  PubMed  CAS  Google Scholar 

  2. Noisakran S, Perng GC. Alternate hypothesis on the pathogenesis of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) in dengue virus infection. Exp Biol Med (Maywood ). 2008;233:401–8.

    Article  CAS  Google Scholar 

  3. WHO. Dengue. Guidelines for diagnosis, treatment, prevention and control (3 rd edn.). 2009.

  4. Rosen L. The Emperor’s New Clothes revisited, or reflections on the pathogenesis of dengue hemorrhagic fever. Am J Trop Med Hyg. 1977;26:337–43.

    PubMed  CAS  Google Scholar 

  5. Halstead SB, Nimmannitya S, Cohen SN. Observations related to pathogenesis of dengue hemorrhagic fever. IV. Relation of disease severity to antibody response and virus recovered. Yale J Biol Med. 1970;42:311–28.

    PubMed  CAS  Google Scholar 

  6. Mongkolsapaya J, Dejnirattisai W, Xu XN, Vasanawathana S, Tangthawornchaikul N, Chairunsri A, et al. Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic fever. Nat Med. 2003;9:921–7.

    Article  PubMed  CAS  Google Scholar 

  7. Halstead SB. Pathogenesis of dengue: challenges to molecular biology. Science. 1988;239:476–81.

    Article  PubMed  CAS  Google Scholar 

  8. Pang T, Cardosa MJ, Guzman MG. Of cascades and perfect storms: the immunopathogenesis of dengue haemorrhagic fever-dengue shock syndrome (DHF/DSS). Immunol Cell Biol. 2007;85:43–5.

    Article  PubMed  CAS  Google Scholar 

  9. Moreno-Altamirano MMB, Sanchez-Garcia FJ, Munoz ML. Non Fc receptor-mediated infection of human macrophages by dengue virus serotype 2. J Gen Virol. 2002;83:1123–30.

    PubMed  CAS  Google Scholar 

  10. Bielefeldt-Ohmann H, Meyer M, Fitzpatrick DR, Mackenzie JS. Dengue virus binding to human leukocyte cell lines: receptor usage differs between cell types and virus strains. Virus Res. 2001;73:81–9.

    Article  PubMed  CAS  Google Scholar 

  11. Vaughn DW, Green S, Kalayanarooj S, Innis BL, Nimmannitya S, Suntayakorn S, et al. Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. J Infect Dis. 2000;181:2–9.

    Article  PubMed  CAS  Google Scholar 

  12. Libraty DH, Young PR, Pickering D, Endy TP, Kalayanarooj S, Green S, et al. High circulating levels of the dengue virus nonstructural protein NS1 early in dengue illness correlate with the development of dengue hemorrhagic fever. J Infect Dis. 2002;186:1165–8.

    Article  PubMed  CAS  Google Scholar 

  13. Endy TP, Nisalak A, Chunsuttitwat S, Vaughn DW, Green S, Ennis FA, et al. 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. 2004;189:990–1000.

    Article  PubMed  Google Scholar 

  14. Guilarde A, Turchi Jr M. J, Feres V, Rocha B, Levi J, Souza V, Boas L, Pannuti C, Martelli C. Dengue and dengue hemorrhagic fever among adults: clinical outcomes related to viremia, serotypes, and antibody response. J Infect Dis. 2008;197:817–24.

    Article  PubMed  Google Scholar 

  15. Rothman AL. Immunity to dengue virus: a tale of original antigenic sin and tropical cytokine storms. Nat Rev Immunol. 2011;11:532–43.

    Article  PubMed  CAS  Google Scholar 

  16. Bonasio R, von Andrian UH. Generation, migration and function of circulating dendritic cells. Curr Opin Immunol. 2006;18:503–11.

    Article  PubMed  CAS  Google Scholar 

  17. Sun P, Fernandez S, Marovich MA, Palmer DR, Celluzzi CM, Boonnak K, et al. Functional characterization of ex vivo blood myeloid and plasmacytoid dendritic cells after infection with dengue virus. Virology. 2009;383:207–15.

    Article  PubMed  CAS  Google Scholar 

  18. Dejnirattisai W, Duangchinda T, Lin CLS, Vasanawathana S, Jones M, Jacobs M, et al. A complex interplay among virus, dendritic cells, T cells, and cytokines in dengue virus infections. J Immunol. 2008;181:5865–74.

    PubMed  CAS  Google Scholar 

  19. Rodriguez-Madoz JR, Bernal-Rubio D, Kaminski D, Boyd K, Fernandez-Sesma A. Dengue virus inhibits the production of type I interferon in primary human dendritic cells. J Virol. 2010;84:4845–50.

    Article  PubMed  CAS  Google Scholar 

  20. Boonnak K, Slike BM, Burgess TH, Mason RM, Wu SJ, Sun P, et al. Role of dendritic cells in antibody-dependent enhancement of dengue virus infection. J Virol. 2008;82:3939–51.

    Article  PubMed  CAS  Google Scholar 

  21. Hosmalin A, Lichtner M, Louis S. Clinical analysis of dendritic cell subsets: the dendritogram. Methods Mol Biol. 2008;415:273–90.

    Article  PubMed  CAS  Google Scholar 

  22. Pichyangkul S, Endy TP, Kalayanarooj S, Nisalak A, Yongvanitchit K, Green S, et al. A blunted blood plasmacytoid dendritic cell response to an acute systemic viral infection is associated with increased disease severity. J Immunol. 2003;171:5571–8.

    PubMed  CAS  Google Scholar 

  23. Tsai JJ, Jen YH, Chang JS, Hsiao HM, Noisakran S, Perng GC. Frequency alterations in key innate immune cell components in the peripheral blood of dengue patients detected by FACS analysis. J Innate Immun. 2011;3:530–40.

    Article  PubMed  CAS  Google Scholar 

  24. Deen JL, Harris E, Wills B, Balmaseda A, Hammond SN, Rocha C, et al. The WHO dengue classification and case definitions: time for a reassessment. Lancet. 2006;368:170–3.

    Article  PubMed  Google Scholar 

  25. Thomas L, Brouste Y, Najioullah F, Hochedez P, Hatchuel Y, Moravie V, et al. Predictors of severe manifestations in a cohort of adult dengue patients. J Clin Virol. 2010;48:96–9.

    Article  PubMed  Google Scholar 

  26. Lanciotti RS, Calisher CH, Gubler DJ, Chang GJ, Vorndam AV. Rapid detection and typing of dengue viruses from clinical samples by using reverse transcriptase-polymerase chain reaction. J Clin Microbiol. 1992;30:545–51.

    PubMed  CAS  Google Scholar 

  27. Vaughn DW, Nisalak A, Solomon T, Kalayanarooj S, Nguyen MD, Kneen R, et al. Rapid serologic diagnosis of dengue virus infection using a commercial capture ELISA that distinguishes primary and secondary infections. Am J Trop Med Hyg. 1999;60:693–8.

    PubMed  CAS  Google Scholar 

  28. Vazquez S, Hafner G, Ruiz D, Calzada N, Guzman MG. Evaluation of immunoglobulin M and G capture enzyme-linked immunosorbent assay Panbio kits for diagnostic dengue infections. J Clin Virol. 2007;39:194–8.

    Article  PubMed  CAS  Google Scholar 

  29. Vuckovic S, Gardiner D, Field K, Chapman GV, Khalil D, Gill D, et al. Monitoring dendritic cells in clinical practice using a new whole blood single-platform TruCOUNT assay. Journal of Immunological Methods. 2004;284:73–87.

    Article  PubMed  CAS  Google Scholar 

  30. Marovich M, Grouard-Vogel G, Louder M, Eller M, Sun W, Wu SJ, et al. Human dendritic cells as targets of dengue virus infection. J Investig Dermatol Symp Proc. 2001;6:219–24.

    Article  PubMed  CAS  Google Scholar 

  31. Nightingale ZD, Patkar C, Rothman AL. Viral replication and paracrine effects result in distinct, functional responses of dendritic cells following infection with dengue 2 virus. J Leukoc Biol. 2008;84:1028–38.

    Article  PubMed  CAS  Google Scholar 

  32. Tsai YT, Chang SY, Lee CN, Kao CL. Human TLR3 recognizes dengue virus and modulates viral replication in vitro. Cell Microbiol. 2009;11:604–15.

    Article  PubMed  CAS  Google Scholar 

  33. Sugiyama T, Hoshino K, Saito M, Yano T, Sasaki I, Yamazaki C, et al. Immunoadjuvant effects of polyadenylic:polyuridylic acids through TLR3 and TLR7. Int Immunol. 2008;20:1–9.

    Article  PubMed  CAS  Google Scholar 

  34. Wang L, Chen RF, Liu JW, Lee IK, Lee CP, Kuo HC, et al. DC-SIGN (CD209) Promoter-336 A/G polymorphism is associated with dengue hemorrhagic fever and correlated to DC-SIGN expression and immune augmentation. PLoS Negl Trop Dis. 2011;5:e934.

    Article  PubMed  CAS  Google Scholar 

  35. Diop OM, Ploquin MJY, Mortara L, Faye A, Jacquelin B, Kunkel D, et al. Plasmacytoid Dendritic Cell Dynamics and Alpha Interferon Production during Simian Immunodeficiency Virus Infection with a Nonpathogenic Outcome. J Virol. 2008;82:5145–52.

    Article  PubMed  CAS  Google Scholar 

  36. Luplertlop N, Misse D, Bray D, Deleuze V, Gonzalez JP, Leardkamolkarn V, et al. Dengue-virus-infected dendritic cells trigger vascular leakage through metalloproteinase overproduction. EMBO Rep. 2006;7:1176–81.

    Article  PubMed  Google Scholar 

  37. La Russa VF, Innis BL. Mechanisms of dengue virus-induced bone marrow suppression. Baillieres Clin Haematol. 1995;8:249–70.

    Article  PubMed  Google Scholar 

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Acknowledgements

We gratefully acknowledge Professor Marie-Christine Béné for her helpful critical comments on the manuscript.

Funding

This work was supported by the French Ministère de l’Enseignement Supérieur et de la Recherche through its financial assistance to EA 4369 RHEM and JE 2503. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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The authors declare that they have no conflict of interest.

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Correspondence to Marcelo De Carvalho Bittencourt.

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De Carvalho Bittencourt, M., Martial, J., Cabié, A. et al. Decreased Peripheral Dendritic Cell Numbers in Dengue Virus Infection. J Clin Immunol 32, 161–172 (2012). https://doi.org/10.1007/s10875-011-9592-9

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  • DOI: https://doi.org/10.1007/s10875-011-9592-9

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