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Citation: Edith Marcial-Juárez,  Julio García-Cordero,  Raúl Antonio Maqueda-Alfaro,  Rafael Eduardo Saucedo-López,  Luvia Enid Sánchez-Torres,  Leticia Cedillo-Barrón,  Leopoldo Flores-Romo. Cutaneous Dengue Virus Inoculation Triggers Strong B Cell Reactions but Contrastingly Poor T Cell Responses [J].VIROLOGICA SINICA.  http://dx.doi.org/10.1007/s12250-020-00213-6

Cutaneous Dengue Virus Inoculation Triggers Strong B Cell Reactions but Contrastingly Poor T Cell Responses

  • Dengue is a global health problem without current specific treatment nor safe vaccines available. While severe dengue is related to pre-existing non-neutralizing dengue virus (DENV) antibodies, the role of T cells in protection or pathology is unclear. Using cutaneous DENV infection in immunocompetent mice we previously showed the generation of PNA+ germinal centers (GCs), now we assessed the activation and proliferation of B and T cells in draining lymph nodes (DLNs). We found a drastic remodelling of DLN compartments from 7 to 14 days post-infection (dpi) with greatly enlarged B cell follicles, occupying almost half of the DLN area compared to ~24% in naïve conditions. Enormous clusters of proliferating (Ki-67+) cells inside B follicles were found 14 dpi, representing ~33% of B cells in DLNs but only ~2% in noninfected mice. Inside GCs, we noticed an important recruitment of tingle body macrophages removing apoptotic cells. In contrast, the percentage of paracortex area and total T cells decreased by 14–16 dpi, compared to controls. Scattered randomly distributed Ki-67+ T cells were found, similar to non-infected mice. CD69 expression by CD4+ and CD8+ T cells was minor, while it was remarkable in B cells, representing 1764.7% of change from basal levels 3 dpi. The apparent lack of T cell responses cannot be attributed to apoptosis since no significant differences were observed compared to noninfected mice. This study shows massive B cell activation and proliferation in DLNs upon DENV infection. In contrast, we found very poor, almost absent CD4+ and CD8+ T cell responses.

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    1. Arkin F (2019) Dengue researcher faces charges in vaccine fiasco.Science 364:320

    2. Aye KS, Charngkaew K, Win N et al (2014) Pathologic highlights of dengue hemorrhagic fever in 13 autopsy cases from Myanmar.Hum Pathol 45:1221–1233

    3. Balakrishnan T, Bela-Ong DB, Toh YX et al (2011) Dengue virus activates polyreactive, natural IgG B cells after primary and secondary infection. PLoS ONE 6:e29430

    4. Bhatt S, Gething PW, Brady OJ et al (2013) The global distribution and burden of dengue. Nature 496:504–507

    5. Blackley S, Kou Z, Chen H et al (2007) Primary human splenic macrophages, but not T or B cells, are the principal target cells for dengue virus infection in vitro. J Virol 81:13325–13334

    6. Buddhari D, Aldstadt J, Endy TP et al (2014) Dengue virus neutralizing antibody levels associated with protection from infection in Thai Cluster studies. PLoS Negl Trop Dis 8:1–10

    7. Burke DS, Scott RM, Johnson DE, Nisalak A (1988) A prospective study of dengue infections in Bangkok. Am J Trop Med Hyg 38:172–180

    8. Cannon MJ, Stott EJ, Taylor G, Askonas BA (1987) Clearance of persistent respiratory syncytial virus infections in immunodeficient mice following transfer of primed T cells. Immunology 62:133–138

    9. Cerny D, Haniffa M, Shin A et al (2014) Selective susceptibility of human skin antigen presenting cells to productive dengue virus infection. PLoS Pathog 10:e1004548

    10. Chandele A, Sewatanon J, Gunisetty S et al (2016) Characterization of human CD8 T cell responses in dengue virus-infected patients from India. J Virol 90:11259–11278

    11. Channappanavar R, Fett C, Zhao J et al (2014) Virus-specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection. J Virol 88:11034–11044

    12. Chatterjee P (2019) Dengvaxia researcher charged. Lancet Infect Dis 19:584–585

    13. Correa ARV, Berbel ACER, Papa MP et al (2015) Dengue virus directly stimulates Polyclonal B cell activation. PLoS ONE 10:1–20

    14. Cyster JG, Schwab SR (2012) Sphingosine-1-phosphate and lymphocyte egress from lymphoid organs. Annu Rev Immunol 30:69–94

    15. Dick OB, San Martín JL, Montoya RH et al (2012) Review: the history of dengue outbreaks in the Americas. Am J Trop Med Hyg 87:584–593

    16. Dung NTP, Le DH, Van TN et al (2010) Timing of CD8+ T cell responses in relation to commencement of capillary leakage in children with dengue. J Immunol 184:7281–7287

    17. Endy TP, Chunsuttiwat S, Nisalak A et al (2002) Epidemiology of inapparent and symptomatic acute dengue virus infection: a prospective study of primary school children in Kamphaeng Phet, Thailand. Am J Epidemiol 156:40–51

    18. Flajnik MF (2018) A cold-blooded view of adaptive immunity. Nat Rev Immunol 18:438–453

    19. Flemming W (1885) Studien über Regeneration der Gewebe. Arch mikr Anat 24:50–91

    20. Friberg H, Bashyam H, Toyosaki-Maeda T et al (2011) Crossreactivity and expansion of dengue-specific T cells during acute primary and secondary infections in humans. Sci Rep 1:1–9

    21. Garcia-Bates TM, Cordeiro MT, Nascimento EJM et al (2013)Association between magnitude of the virus-specific plasmablast response and disease severity in dengue patients. J Immunol 190:80–87

    22. Gawoski JM, Ooi WW (2003) Dengue fever mimicking plasma cell leukemia. Arch Pathol Lab Med 127:1026–1027

    23. Glaum MC, Narula S, Song D et al (2009) Toll-like receptor 7-induced naive human B-cell differentiation and immunoglobulin production. J Allergy Clin Immunol 123:224.e4–230.e4

    24. Godoy-Lozano EE, Téllez-Sosa J, Sánchez-González G et al (2016)Lower IgG somatic hypermutation rates during acute dengue virus infection is compatible with a germinal center-independent B cell response. Genome Med 8:1–19

    25. Graham RR, Juffrie M, Tan R et al (1999) A prospective seroepidemiologic study on dengue in children four to nine years of age in Yogyakarta, Indonesia I. Studies in 1995–1996. Am J Trop Med Hyg 61:412–419

    26. Green S, Pichyangkul S, Vaughn DW et al (1999) Early CD69 expression on peripheral blood lymphocytes from children with dengue hemorrhagic fever. J Infect Dis 180:1429–1435

    27. Halstead SB (1970) Observations related to pathogensis of dengue hemorrhagic fever. VI. Hypotheses and discussion. Yale J Biol Med 42:350–362

    28. Halstead SB, O’Rourke EJ (1977) Antibody-enhanced dengue virus infection in primate leukocytes. Nature 265:739–741

    29. Hardie DL, Johnson GD, Khan M, MacLennan ICM (1993) Quantitative analysis of molecules which distinguish functional compartments within germinal centers. Eur J Immunol 23:997–1004

    30. Hor JL, Whitney PG, Zaid A et al (2015) spatiotemporally distinct interactions with dendritic cell subsets facilitates CD4+ and CD8+ T cell activation to localized viral infection. Immunity 43:554–565

    31. Jampangern W, Vongthoung K, Jittmittraphap A et al (2007)Characterization of atypical lymphocytes and immunophenotypes of lymphocytes in patients with dengue virus infection.Asian Pac J Allergy Immunol 25:27–36

    32. Jellison ER, Guay HM, Szomolanyi-Tsuda E, Welsh RM (2007)Dynamics and magnitude of virus-induced polyclonal B cell activation mediated by BCR-independent presentation of viral antigen. Eur J Immunol 37:119–128

    33. MacLennan IC (1994) Germinal centers. Annu Rev Immunol 12:117–139

    34. Malavige GN, Ogg GS (2013) T cell responses in dengue viral infections. J Clin Virol 58:605–611

    35. Marcial-Juárez E, Yam-Puc JC, Cedillo-Barrón L et al (2017)Travelling with dengue: from the skin to the nodes. In:Aparecida Sperança M (ed) Dengue: immunopathology and control strategies, 1st edn. IntechOpen Limited, London, pp 27–42

    36. Mathew A, Kurane I, Green S et al (1999) Impaired T cell proliferation in acute dengue infection. J Immunol 162:5609–5615

    37. Mongkolsapaya J, Dejnirattisai W, Xu X et al (2003) Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic fever. Nat Med 9:921–927

    38. Mongkolsapaya J, Duangchinda T, Dejnirattisai W et al (2006) T cell responses in dengue hemorrhagic fever: are cross-reactive T cells suboptimal? J Immunol 176:3821–3829

    39. Ndhlovu ZM, Kamya P, Mewalal N et al (2015) Magnitude and kinetics of CD8+ T cell activation during hyperacute HIV infection impact viral set point. Immunity 43:591–604

    40. Nightingale ZD, Patkar C, Rothman AL (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

    41. Nivarthi UK, Tu HA, Delacruz MJ et al (2019) Longitudinal analysis of acute and convalescent B cell responses in a human primary dengue serotype 2 infection model. EBioMedicine 41:465–478

    42. Rivino L (2016) T cell immunity to dengue virus and implications for vaccine design. Expert Rev Vaccines 15:443–453

    43. Rothman AL (2004) Dengue: defining protective versus pathologic immunity. J Clin Invest 113:946–951

    44. Rush B (1789) An account of the bilious remitting fever, as it appeared in Philadelphia in the summer and autumn of the year 1780, Medical In. Prichard and Hall, Philadelphia Sabin AB (1952) Research on Dengue during World War II 1. Am J Trop Med Hyg 1:30–50

    45. Sangkawibha N, Rojanasuphot S, Ahandrik S et al (1984) Risk factors in dengue shock syndrome: a prospective epidemiologic study in Rayong, Thailand: I. The 1980 outbreak. Am J Epidemiol 120:653–669

    46. Screaton G, Mongkolsapaya J, Yacoub S, Roberts C (2015) New insights into the immunopathology and control of dengue virus infection. Nat Rev Immunol 15:745–759

    47. Slütter B, Pewe LL, Kaech SM, Harty JT (2013) Lung airwaysurveilling CXCR3hi Memory CD8+ T cells are critical for protection against influenza A virus. Immunity 39:939–948

    48. Taylor PM, Askonas BA (1986) Influenza nucleoprotein-specific cytotoxic T-cell clones are protective in vivo. Immunology 58:417–420

    49. WHO (2012) Global strategy for dengue prevention and control 2012–2020. WHO Press, Geneva WHO (2019) Dengue and severe dengue. In: WHO. https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue. Accessed 30 Sep 2019

    50. Wrammert J, Onlamoon N, Akondy RS et al (2012) Rapid and massive virus-specific plasmablast responses during acute dengue virus infection in humans. J Virol 86:2911–2918

    51. Wu S-JJ, Grouard-Vogel G, Sun W et al (2000) Human skin Langerhans cells are targets of dengue virus infection. Nat Med 6:816–820

    52. Yam-Puc JC, García-Cordero J, Calderón-Amador J et al (2015)Germinal center reaction following cutaneous dengue virus infection in immune-competent mice. Front Immunol 6:1–9

    53. Yap KL, Ada GL, McKenzie IFC (1978) Transfer of specific cytotoxic T lymphocytes protects mice inoculated with influenza virus. Nature 273:238–239

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    Cutaneous Dengue Virus Inoculation Triggers Strong B Cell Reactions but Contrastingly Poor T Cell Responses

      Corresponding author: Edith Marcial-Juárez, edith.mjuarez@gmail.com
      Corresponding author: Leopoldo Flores-Romo, lefloresromo@gmail.com
    • 1 Department of Cell Biology, Center for Advanced Research (CINVESTAV-IPN), The National Polytechnic Institute, 07360 Mexico City, Mexico
    • 2 Department of Molecular Biomedicine, Center for Advanced Research (CINVESTAV-IPN), The National Polytechnic Institute, 07360 Mexico City, Mexico
    • 3 Immunology Department, The National School of Biological Sciences (ENCB-IPN), The National Polytechnic Institute, 11340 Mexico City, Mexico

    Abstract: Dengue is a global health problem without current specific treatment nor safe vaccines available. While severe dengue is related to pre-existing non-neutralizing dengue virus (DENV) antibodies, the role of T cells in protection or pathology is unclear. Using cutaneous DENV infection in immunocompetent mice we previously showed the generation of PNA+ germinal centers (GCs), now we assessed the activation and proliferation of B and T cells in draining lymph nodes (DLNs). We found a drastic remodelling of DLN compartments from 7 to 14 days post-infection (dpi) with greatly enlarged B cell follicles, occupying almost half of the DLN area compared to ~24% in naïve conditions. Enormous clusters of proliferating (Ki-67+) cells inside B follicles were found 14 dpi, representing ~33% of B cells in DLNs but only ~2% in noninfected mice. Inside GCs, we noticed an important recruitment of tingle body macrophages removing apoptotic cells. In contrast, the percentage of paracortex area and total T cells decreased by 14–16 dpi, compared to controls. Scattered randomly distributed Ki-67+ T cells were found, similar to non-infected mice. CD69 expression by CD4+ and CD8+ T cells was minor, while it was remarkable in B cells, representing 1764.7% of change from basal levels 3 dpi. The apparent lack of T cell responses cannot be attributed to apoptosis since no significant differences were observed compared to noninfected mice. This study shows massive B cell activation and proliferation in DLNs upon DENV infection. In contrast, we found very poor, almost absent CD4+ and CD8+ T cell responses.

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