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Understanding and exploiting dendritic cells in human immunodeficiency virus infection using the nonhuman primate model

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Abstract

Dendritic cells (DC) are pivotal cells in the innate immune system. Recent interest in the role of DC in human immunodeficiency virus (HIV) pathogenesis has increased with the finding that both myeloid (mDC) and plasmacytoid DC (pDC) are lost from blood during infection, associated with progression to disease. DC are also being studied intensively for their capacity to stimulate robust virus-specific immunity as vaccines. Here we discuss our work in these contrasting fields of DC biology using the rhesus macaque nonhuman primate model. We focus on studies of DC dynamics in lymphoid tissues during pathogenic simian immunodeficiency virus (SIV) infection, DC trafficking in health and disease, DC-based vaccination and the use of autologous virus as antigen for stimulation of virus-specific T cells.

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References

  1. Shortman K, Liu YJ: Mouse and human dendritic cell subtypes. Nat Rev Immunol 2002;2: 151–161.

    Article  PubMed  CAS  Google Scholar 

  2. Banchereau J, Briere F, Caux C, et al: Immunobiology of dendritic cells. Annu Rev Immunol 2000;18: 767–811.

    Article  PubMed  CAS  Google Scholar 

  3. Colonna M, Trinchieri G, Liu YJ: Plasmacytoid dendritic cells in immunity. Nat Immunol 2004;5: 1219–1226.

    Article  PubMed  CAS  Google Scholar 

  4. Cella M, Jarrossay D, Facchetti F, et al: Plasmacy toid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat Med 1999;5: 919–923.

    Article  PubMed  CAS  Google Scholar 

  5. Yoneyama H, Matsuno K, Zhang Y, et al: Evidence for recruitment of plasmacytoid dendritic cell precursors to inflamed lymph nodes through high endothelial venules. Int Immunol 2004;16: 915–928.

    Article  PubMed  CAS  Google Scholar 

  6. Yoneyama H, Matsuno K, Matsushimaa K: Migration of dendritic cells. Int J Hematol 2005;81: 204–207.

    Article  PubMed  CAS  Google Scholar 

  7. Schlecht G, Garcia S, Escriou N, Freitas AA, Leclerc C, Dadaglio G: Murine plasmacytoid dendritic cells induce effector/memory CD8+ T-cell responses in vivo after viral stimulation. Blood 2004;104: 1808–1815.

    Article  PubMed  CAS  Google Scholar 

  8. Yoneyama H, Matsuno K, Toda E, et al: Plasmacytoid DCs help lymph node DCs to induce anti-HSV CTLs. J Exp Med 2005;202: 425–435.

    Article  PubMed  CAS  Google Scholar 

  9. Pope M, Betjes MG, Romani N, et al: Conjugatexs of dendritic cells and memory T lymphocytes from skin facilitate productive infection with HIV-1. Cell 1994;78: 389–398.

    Article  PubMed  CAS  Google Scholar 

  10. Geijtenbeek TB, Kwon DS, Torensma R, et al: DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell 2000;100: 587–597.

    Article  PubMed  CAS  Google Scholar 

  11. Hu J, Gardner MB, Miller CJ: Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells. J Virol 2000;74: 6087–6095.

    Article  PubMed  CAS  Google Scholar 

  12. Turville SG, Cameron PU, Handley A, et al: Diversity of receptors binding HIV on dendritic cell subsets. Nat Immunol 2002;3: 975–983.

    Article  PubMed  CAS  Google Scholar 

  13. Chehimi J, Campbell DE, Azzoni L, et al: Persistent decreases in blood plasmacytoid dendritic cell number and function despite effective highly active antiretroviral therapy and increased blood myeloid dendritic cells in HIV-infected individuals. J Immunol 2002;168: 4796–4801.

    PubMed  CAS  Google Scholar 

  14. Grassi F, Hosmalin A, McIlroy D, Calvez V, Debre P, Autran B: Depletion in blood CD11c-positive dendritic cells from HIV-infected patients. Aids 1999;13: 759–766.

    Article  PubMed  CAS  Google Scholar 

  15. Donaghy H, Pozniak A, Gazzard B, et al: Loss of blood CD11c(+) myeloid and CD11c(−) plasmacytoid dendritic cells in patients with HIV-1 infection correlates with HIV-1 RNA virus load. Blood 2001;98: 2574–2576.

    Article  PubMed  CAS  Google Scholar 

  16. Pacanowski J, Kahi S, Baillet M, et al: Reduced blood CD123+ (lymphoid) and CD11c+ (myeloid) dendritic cell numbers in primary HIV-1 infection. Blood 2001;98: 3016–3021.

    Article  PubMed  CAS  Google Scholar 

  17. Soumelis V, Scott J, Ghevas F, et al: Depletion of circulating natural type 1 interferon-producing cells in HIV-infected AIDS patients. Blood 2001;98: 906–912.

    Article  PubMed  CAS  Google Scholar 

  18. Barron MA, Blyveis N, Palmer BE, MaWhinney S, Wilson CC: Influence of plasma viremia on defects in number and immunophenotype of blood dendritic cell subsets in human immunodeficiency virus 1-infected individuals. J Infect Dis 2003;187: 26–37.

    Article  PubMed  Google Scholar 

  19. Lu W, Arraes LC, Ferreira WT, Andrieu JM: Therapeutic dendritic-cell vaccine for chronic HIV-1 infection. Nat Med 2004;10: 1359–1365.

    Article  PubMed  CAS  Google Scholar 

  20. Lu W, Wu X, Lu Y, Guo W, Andrieu JM: Therapeutic dendritic-cell vaccine for simian AIDS. Nat Med 2003;9: 27–32.

    Article  PubMed  CAS  Google Scholar 

  21. Coates PT, Barratt-Boyes SM, Donnenberg AD, Morelli AE, Murphey-Corb M, Thomson AW: Strategies for preclinical evaluation of dendritic cell subsets for promotion of transplant tolerance in the nonhuman primate. Hum Immunol 2002;63: 955–965.

    Article  PubMed  CAS  Google Scholar 

  22. Coates PT, Barratt-Boyes SM, Zhang L, et al: Dendritic cell subsets in blood and lymphoid tissue of rhesus monkeys and their mobilization with Flt3 ligand. Blood 2003;102: 2513–2521.

    Article  PubMed  CAS  Google Scholar 

  23. Teleshova N, Jones J, Kenney J, et al: Short-term Flt3L treatment effectively mobilizes functional macaque dendritic cells. J Leukoc Biol 2004;75: 1102–1110.

    Article  PubMed  CAS  Google Scholar 

  24. Barratt-Boyes SM, Thomson AW: Dendritic cells: tools and targets for transplant tolerance. Am J Transpl 2005;5: 2807–2813.

    Article  CAS  Google Scholar 

  25. Zimmer MI, Larregina AT, Castillo CM, et al: Disrupted homeostasis of Langerhans cells and interdigitating dendritic cells in monkeys with AIDS. Blood 2002;99: 2859–2868.

    Article  PubMed  CAS  Google Scholar 

  26. Wilson NS, El-Sukkari D, Belz GT, et al: Most lymphoid organ dendritic cell types are phenotypically and functionally immature. Blood 2003;102: 2187–2194.

    Article  PubMed  CAS  Google Scholar 

  27. Fonteneau JF, Larsson M, Beignon AS, et al: Human immunodeficiency virus type 1 activates plasmacytoid dendritic cells and concomitantly induces the bystander maturation of myeloid dendritic cells. J Virol 2004;78: 5223–5232.

    Article  PubMed  CAS  Google Scholar 

  28. McKenna K, Beignon AS, Bhardwaj N: Plasmacytoid dendritic cells: linking innate and adaptive immunity. J Virol 2005;79: 17–27.

    Article  PubMed  CAS  Google Scholar 

  29. Abel K, Alegria-Hartman MJ, Rothaeusler K, Marthas M, Miller CJ: The relationship between simian immunodeficiency virus RNA levels and the mRNA levels of alpha/beta interferons (IFN-alpha/beta) and IFN-alpha/beta-inducible Mx in lymphoid tissues of rhesus macaques during acute and chronic infection. J Virol 2002;76: 8433–8445.

    Article  PubMed  CAS  Google Scholar 

  30. Reinhart TA, Fallert BA, Pfeifer ME, et al: Increased expression of the inflammatory chemokine CXC chemokine ligand 9/monokine induced by interferon-gamma in lymphoid tissues of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome. Blood 2002;99: 3119–3128.

    Article  PubMed  CAS  Google Scholar 

  31. Lore K, Sonnerborg A, Brostrom C, et al: Accumulation of DC-SIGN+CD40+ dendritic cells with reduced CD80 and CD86 expression in lymphoid tissue during acute HIV-1 infection. Aids 2002;16: 683–692.

    Article  PubMed  Google Scholar 

  32. Barratt-Boyes SM, Zimmer MI, Harshyne L: Changes in dendritic cell migration and activation during SIV infection suggest a role in initial viral spread and eventual immunosuppression. J Med Primatol 2002;31: 186–193.

    Article  PubMed  CAS  Google Scholar 

  33. Donaghy H, Gazzard B, Gotch F, Patterson S: Dysfunction and infection of freshly isolated blood myeloid and plasmacytoid dendritic cells in patients infected with HIV-1. Blood 2003;101: 4505–4511.

    Article  PubMed  CAS  Google Scholar 

  34. Thiebot H, Louache F, Vaslin B, et al: Early and persistent bone marrow hematopoiesis defect in simian/human immunodeficiency virus-infected macaques despite efficient reduction of viremia by highly active antiretroviral therapy during primary infection. J Virol 2001;75: 11594–11602.

    Article  PubMed  CAS  Google Scholar 

  35. Yamakami K, Honda M, Takei M, et al: Early bone marrow hematopoietic defect in simian/human immunodeficiency virus C2/1-infected macaques and relevance to advance of disease. J Virol 2004;78: 10906–10910.

    Article  PubMed  CAS  Google Scholar 

  36. Thiebot H, Vaslin B, Derdouch S, et al: Impact of bone marrow hematopoiesis failure on T-cell generation during pathogenic simian immunodeficiency virus infection in macaques. Blood 2005;105: 2403–2409.

    Article  PubMed  CAS  Google Scholar 

  37. Hu J, Miller CJ, O'Doherty U, Marx PA, Pope M: The dendritic cell-T cell milieu of the lymphoid tissue of the tonsil provides a locale in which SIV can reside and propagate at chronic stages of infection. AIDS Res Hum Retroviruses 1999; 15: 1305–1314.

    Article  PubMed  CAS  Google Scholar 

  38. Fugier-Vivier I, Servet-Delprat C, Rivailler P, Rissoan MC, Liu YJ, Rabourdin-Combe C. Measles virus supresses cell-mediated immunity by interfering with the survival and functions of dendritic and T cells. J Exp Med 1997;186:813–823.

    Article  PubMed  CAS  Google Scholar 

  39. Vidalain PO, Azocar O, Lamouille B, Astier A, Rabourdin-Combe C, Servet-Delprat C. Measles virus induces functional TRAIL production by human dendritic cells. J Virol 2000;74: 556–559.

    Article  PubMed  CAS  Google Scholar 

  40. Muller DB, Raftery MJ, Kather A, Giese T, Schonrich G: Frontline: Induction of apoptosis and modulation of c-FLIPL and p53 in immature dendritic cells infected with herpes simplex virus. Eur J Immunol 2004;34:941–951.

    Article  PubMed  CAS  Google Scholar 

  41. Herbeuval JP, Boasso A, Grivel JC et al: TNF-related apoptosis inducing ligand (TRAIL) in HIV-1-infected patients and its in vitro production by antigen-presenting cells. Blood 2005;105: 2458–2464.

    Article  PubMed  CAS  Google Scholar 

  42. Herbeuval JP, Grivel JC, Boasso A, et al: CD4+ T-cell death induced by infectious and noninfectious HIV-1; role of type 1 interferon-dependent, TRAIL/DR5-mediated apoptosis. Blood 2005;106: 3524–3531.

    Article  PubMed  CAS  Google Scholar 

  43. Herbeuval JP, Hardy AW, Boasso A, et al: Regulation of TNF-related apoptosis-inducing ligand on primary CD4+ T cells by HIV-1: role of type I IFN-producing plasmacytoid dendritic cells. Proc Natl Acad Sci USA 2005;102: 13974–13979.

    Article  PubMed  CAS  Google Scholar 

  44. Lichtner M, Maranon C, Vidalain PO, et al: HIV type 1-infected dendritic cells induce apoptotic death in infected and uninfected primary CD4 T lymphocytes. AIDS Res Hum Retroviruses 2004;20: 175–182.

    Article  PubMed  CAS  Google Scholar 

  45. Barratt-Boyes SM, Henderson RA, Finn OJ: Chimpanzee dendritic cells with potent immunostimulatory function can be propagated from peripheral blood. Immunology 1996;87: 528–534.

    Article  PubMed  CAS  Google Scholar 

  46. Enose Y, Ibuki K, Tamaru K, et al: Replication capacity of simian immunodeficiency virus in cultured macaque macrophages and dendritic cells is not prerequisite for intravaginal transmission of the virus in macaques. J Gen Virol 1999;80(Pt 4): 847–855.

    PubMed  CAS  Google Scholar 

  47. O'Doherty U, Ignatius R, Bhardwaj N, Pope M: Generation of monocyte-derived dendritic cells from precursors in rhesus macaque blood. J Immunol Methods 1997;207: 185–194.

    Article  PubMed  Google Scholar 

  48. Pinchuk LM, Grouard-Vogel G, Magaletti DM, Doty RT, Andrews RG, Clark EA. Isolation and characterization of macaque dendritic cells from CD34(+) bone marrow progenitors. Cell Immunol 1999;196: 34–40.

    Article  PubMed  CAS  Google Scholar 

  49. Barratt-Boyes SM, Zimmer MI, Harshyne LA, et al: Maturation and trafficking of monocyte-derived dendritic cells in monkeys: implications for dendritic cell-based vaccines. J Immunol 2000;164: 2487–2495.

    PubMed  CAS  Google Scholar 

  50. Barratt-Boyes SM, Watkins SC, Finn OJ: In vivo migration of dendritic cells differentiated in vitro: a chimpanzee model. J Immunol 1997;158: 4543–4547.

    PubMed  CAS  Google Scholar 

  51. Barratt-Boyes SM, Watkins SC, Finn OJ: Migration of cultured chimpanzee dendritic cells following intravenous and subcutaneous injection. Adv Exp Med Biol 1997;417: 71–75.

    PubMed  CAS  Google Scholar 

  52. Lisziewicz J, Gabrilovich DI, Varga G et al: Induction of potent human immunodeficiency virus type 1-specific T-cell-restricted immunity by genetically modified dendritic cells. J Virol 2001;75: 7621–7628.

    Article  PubMed  CAS  Google Scholar 

  53. Villamide-Herrera L, Ignatius R, Eller MA, et al: Macaque dendritic cells infected with SIV-recombinant canarypox ex vivo induce SIV-specific immune responses in vivo. AIDS Res Hum Retroviruses 2004;20:871–884.

    Article  PubMed  CAS  Google Scholar 

  54. De Vries IJ, Krooshoop DJ, Scharenborg NM, et al: Effective migration of antigen-pulsed dendritic cells to lymph nodes in melanoma patients is determined by their maturation state. Cancer Res 2003;63: 12–17.

    PubMed  Google Scholar 

  55. Brown K, Gao W, Alber S, et al: Adenovirus-transduced dendritic cells injected into skin or lymph node prime potent simian immunodeficiency virus-specific T cell immunity in monkeys. J Immunol 2003;171: 6875–6882.

    PubMed  CAS  Google Scholar 

  56. Barratt-Boyes SM, Figdor CG: Current issues in delivering DCs for immunotherapy. Cytotherapy 2004;6: 105–110.

    Article  PubMed  CAS  Google Scholar 

  57. Zhu Y, Koo K, Bradshaw JD, et al: Macaque bloodderived antigen-presenting cells elicit SIV-specific immune responses. J Med Primatol 2000; 29: 182–192.

    Article  PubMed  CAS  Google Scholar 

  58. Nehete PN, Chitta S, Hossain MM, et al: Protection against chronic infection and AIDS by an HIV envelope peptide-cocktail vaccine in a pathogenic SHIV-rhesus model. Vaccine 2001;20: 813–825.

    Article  PubMed  CAS  Google Scholar 

  59. Nehete PN, Nehete BP, Manuri P, Hill L, Palmer JL, Sastry KJ. Protection by dendritic cells-based HIV synthetic peptide cocktail vaccine: preclinical studies in the SHIV-rhesus model. Vaccine 2005;23: 2154–2159.

    Article  PubMed  CAS  Google Scholar 

  60. Zhong L, Granelli-Piperno A, Choi Y, Steinman RM: Recombinant adenovirus is an efficient and non-perturbing genetic vector for human dendritic cells. Eur J Immunol 1999;29: 964–972.

    Article  PubMed  CAS  Google Scholar 

  61. Shiver JW, Fu TM, Chen L, et al: Replication-incompetent adenoviral vaccine vector elicits effective antiimmunodeficiency-virus immunity. Nature 2002;415: 331–335.

    Article  PubMed  CAS  Google Scholar 

  62. MacDonald GH, Johnston RE: Role of dendritic cell targeting in Venezuelan equine encephalitis virus pathogenesis. J Virol 2000;74: 914–922.

    Article  PubMed  CAS  Google Scholar 

  63. Lisziewicz J, Trocio J, Whitman L, et al: DermaVir: a novel topical vaccine for HIV/AIDS. J Invest Dermatol 2005;124: 160–169.

    Article  PubMed  CAS  Google Scholar 

  64. Barratt-Boyes SM, Soloff AC, Gao W, et al: Broad cellular immunity with robust memory responses to simian immunodeficiency virus following serial vaccination with adenovirus 5- and 35-based vectors. J Gen Virol 2006;87: 139–149.

    Article  PubMed  CAS  Google Scholar 

  65. Reyes-Sandoval A, Fitzgerald JC, Grant R, et al: Human immunodeficiency virus type 1-specific immune responses in primates upon sequential immunization with adenoviral vaccine carriers of human and simian serotypes. J Virol 2004;78: 7392–7399.

    Article  PubMed  CAS  Google Scholar 

  66. Shiver JW, Emini EA: Recent advances in the development of HIV-1 vaccines using replication-incompetent adenovirus vectors. Annu Rev Med 2004;55: 355–372.

    Article  PubMed  CAS  Google Scholar 

  67. Goulder PJ, Watkins DI HIV and SIV CTL escape: implications for vaccine design. Nat Rev Immunol 2004;4: 630–640.

    Article  PubMed  CAS  Google Scholar 

  68. Gilboa E, Vieweg J: Cancer immunotherapy with mRNA-transfected dendritic cells. Immunol Rev 2004; 199: 251–263.

    Article  PubMed  CAS  Google Scholar 

  69. Sullenger BA, Gilboa E: Emerging clinical applications of RNA. Nature 2002;418: 252–258.

    Article  PubMed  CAS  Google Scholar 

  70. Van Gulck ER, Ponsaerts P, Heyndrickx L, et al: Efficient stimulation of HIV-1-specific T cells using dendritic cells electroporated with mRNA encoding autologous HIV-1 Gag and Env proteins. Blood 2006;107: 1818–1827.

    Article  PubMed  CAS  Google Scholar 

  71. Weissman D, Ni H, Scales D, et al: HIV gag mRNA transfection of dendritic cells (DC) delivers encoded antigen to MHC class I and II molecules, causes DC maturation, and induces a potent human in vitro primary immune response. J Immunol 2000;165: 4710–4717.

    PubMed  CAS  Google Scholar 

  72. Kavanagh DG, Kaufmann DE, Sunderji S, et al: Expansion of HIV-specific CD4+ and CD8+ T cells by dendritic cells transfected with mRNA encoding cytoplasm-or lysosome-targeted Nef. Blood 2006;107: 1963–1969.

    Article  PubMed  CAS  Google Scholar 

  73. Fonteneau JF, Larsson M, Bhardwaj N: Interactions between dead cells and dendritic cells in the induction of antiviral CTL responses. Curr Opin Immunol 2002;14: 471–477.

    Article  PubMed  CAS  Google Scholar 

  74. Harshyne LA, Zimmer MI, Watkins SC, Barratt-Boyes SM: A role for class A scavenger receptor in dendritic cell nibbling from live cells. J Immunol 2003;170: 2302–2309.

    PubMed  CAS  Google Scholar 

  75. Harshyne LA, Watkins SC, Gambotto A, Barratt-Boyes SM: Dendritic cells acquire antigens from live cells for cross-presentation to CTL. J Immunol 2001;166: 3717–3723.

    PubMed  CAS  Google Scholar 

  76. Maranon C, Desoutter JF, Hoeffel G, Cohen W, Hanau D, Hosmalin A: Dendritic cells cross-present HIV antigens from live as well as apoptotic infected CD4+ T lymphocytes. Proc Natl Acad Sci USA 2004;101: 6092–6097.

    Article  PubMed  CAS  Google Scholar 

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Barratt-Boyes, S.M., Brown, K.N., Melhem, N. et al. Understanding and exploiting dendritic cells in human immunodeficiency virus infection using the nonhuman primate model. Immunol Res 36, 265–274 (2006). https://doi.org/10.1385/IR:36:1:265

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