Monocyte Recruitment to the Dermis and Differentiation to Dendritic Cells Increases the Targets for Dengue Virus Replication

English version České info

The skin and its immune cells are an important barrier against invading pathogens. Dengue is a major public health problem worldwide, with no specific therapeutic or vaccine available. Aedes mosquitoes transmit dengue virus (DENV) to humans via the skin when taking a blood meal. Previous studies have examined DENV infection only in the epidermis, the uppermost layer of the skin, but no information existed about DENV infection in the dermis, the layer below that contains blood vessels. We established a model of DENV infection in the skin of mouse ears, as biopsies from naturally-infected human skin are unavailable. The normal dermis contains classical dendritic cells (DCs) and macrophages, which we found to be the initial targets of DENV infection. Monocytes that circulate in the blood were then recruited to the dermis and differentiated to monocyte-derived DCs, an inflammatory DC subset. These newly-recruited monocytes and monocyte-derived DCs became DENV-infected in a second wave and then were the major targets for DENV replication. Our study identifies how DENV exploits the immune response by infecting cells that are recruited to the skin as part of antiviral defense. These results should help future research to develop new strategies for vaccination and therapeutics against dengue.

Vyšlo v časopise: Monocyte Recruitment to the Dermis and Differentiation to Dendritic Cells Increases the Targets for Dengue Virus Replication. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004541
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004541

Souhrn

Zdroje

1. PasparakisM, HaaseI, NestleFO (2014) Mechanisms regulating skin immunity and inflammation. Nat Rev Immunol 14: 289–301.

2. AlvarezD, VollmannEH, von AndrianUH (2008) Mechanisms and consequences of dendritic cell migration. Immunity 29: 325–342.

3. GeissmannF, ManzMG, JungS, SiewekeMH, MeradM, et al. (2010) Development of monocytes, macrophages, and dendritic cells. Science 327: 656–661.

4. MeradM, ManzMG, KarsunkyH, WagersA, PetersW, et al. (2002) Langerhans cells renew in the skin throughout life under steady-state conditions. Nat Immunol 3: 1135–1141.

5. BurschLS, WangL, IgyartoB, KissenpfennigA, MalissenB, et al. (2007) Identification of a novel population of Langerin+ dendritic cells. J Exp Med 204: 3147–3156.

6. GinhouxF, CollinMP, BogunovicM, AbelM, LeboeufM, et al. (2007) Blood-derived dermal langerin+ dendritic cells survey the skin in the steady state. J Exp Med 204: 3133–3146.

7. NaikSH, MetcalfD, van NieuwenhuijzeA, WicksI, WuL, et al. (2006) Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes. Nat Immunol 7: 663–671.

8. OnaiN, Obata-OnaiA, SchmidMA, OhtekiT, JarrossayD, et al. (2007) Identification of clonogenic common Flt3+M-CSFR+ plasmacytoid and conventional dendritic cell progenitors in mouse bone marrow. Nat Immunol 8: 1207–1216.

9. NaikSH, SatheP, ParkHY, MetcalfD, ProiettoAI, et al. (2007) Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo. Nat Immunol 8: 1217–1226.

10. LiuK, VictoraGD, SchwickertTA, GuermonprezP, MeredithMM, et al. (2009) In vivo analysis of dendritic cell development and homeostasis. Science 324: 392–397.

11. Ginhoux F, Liu K, Helft J, Bogunovic M, Greter M, et al. (2009) The origin and development of nonlymphoid tissue CD103+ DCs. J Exp Med: 3115–3130.

12. BedouiS, WhitneyPG, WaithmanJ, EidsmoL, WakimL, et al. (2009) Cross-presentation of viral and self antigens by skin-derived CD103+ dendritic cells. Nat Immunol 10: 488–495.

13. HenriS, PoulinLF, TamoutounourS, ArdouinL, GuilliamsM, et al. (2010) CD207+ CD103+ dermal dendritic cells cross-present keratinocyte-derived antigens irrespective of the presence of Langerhans cells. J Exp Med 207: 189–206.

14. GinhouxF, TackeF, AngeliV, BogunovicM, LoubeauM, et al. (2006) Langerhans cells arise from monocytes in vivo. Nat Immunol 7: 265–273.

15. ShiC, PamerEG (2011) Monocyte recruitment during infection and inflammation. Nat Rev Immunol 11: 762–774.

16. LeonB, Lopez-BravoM, ArdavinC (2007) Monocyte-derived dendritic cells formed at the infection site control the induction of protective T helper 1 responses against Leishmania. Immunity 26: 519–531.

17. TamoutounourS, GuilliamsM, Montanana SanchisF, LiuH, TerhorstD, et al. (2013) Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin. Immunity 39: 925–938.

18. BhattS, GethingPW, BradyOJ, MessinaJP, FarlowAW, et al. (2013) The global distribution and burden of dengue. Nature 496: 504–507.

19. Pierson TC, Diamond MS (2013) Flaviviruses. In: Knipe DM, Howley PM, editors. Fields Virology. Sixth ed. Philadelphia: Lippincott Williams and Wilkins.

20. HalsteadSB (2007) Dengue. Lancet 370: 1644–1652.

21. KyleJL, BeattyPR, HarrisE (2007) Dengue virus infects macrophages and dendritic cells in a mouse model of infection. J Infect Dis 195: 1808–1817.

22. DurbinA, VargasMJ, ThumarB, HammondSN, GordonG, et al. (2008) Phenotyping of peripheral blood mononuclear cells during acute dengue illness demonstrates infection and increased activation of monocytes in severe cases compared to classic dengue fever. Virology 376: 429–435.

23. SunP, FernandezS, MarovichMA, PalmerDR, CelluzziCM, et al. (2009) Functional characterization of ex vivo blood myeloid and plasmacytoid dendritic cells after infection with dengue virus. Virology 383: 207–215.

24. WuSJ, Grouard-VogelG, SunW, MascolaJR, BrachtelE, et al. (2000) Human skin Langerhans cells are targets of dengue virus infection. Nat Med 6: 816–820.

25. Limon-FloresAY, Perez-TapiaM, Estrada-GarciaI, VaughanG, Escobar-GutierrezA, et al. (2005) Dengue virus inoculation to human skin explants: an effective approach to assess in situ the early infection and the effects on cutaneous dendritic cells. Int J Exp Pathol 86: 323–334.

26. FinkK, NgC, NkenfouC, VasudevanSG, van RooijenN, et al. (2009) Depletion of macrophages in mice results in higher dengue virus titers and highlights the role of macrophages for virus control. Eur J Immunol 39: 2809–2821.

27. GuzmanMG, AlvarezM, HalsteadSB (2013) Secondary infection as a risk factor for dengue hemorrhagic fever/dengue shock syndrome: an historical perspective and role of antibody-dependent enhancement of infection. Arch Virol 158: 1445–1459.

28. RothmanAL (2011) Immunity to dengue virus: a tale of original antigenic sin and tropical cytokine storms. Nat Rev Immunol 11: 532–543.

29. BalsitisSJ, WilliamsKL, LachicaR, FloresD, KyleJL, et al. (2010) Lethal antibody enhancement of dengue disease in mice is prevented by Fc modification. PLoS Pathog 6: e1000790.

30. ZellwegerRM, PrestwoodTR, ShrestaS (2010) Enhanced infection of liver sinusoidal endothelial cells in a mouse model of antibody-induced severe dengue disease. Cell Host Microbe 7: 128–139.

31. ShrestaS, KyleJL, SniderHM, BasanavapatnaM, BeattyR, et al. (2004) Interferon-dependent immunity is essential for resistance to primary dengue virus infection in mice, whereas T and B cell-dependent immunity is less critical. J Virol 78: 2701–2710.

32. AshourJ, MorrisonJ, Laurent-RolleM, Belicha-VillanuevaA, PlumleeCR, et al. (2010) Mouse STAT2 restricts early dengue virus replication. Cell Host Microbe 8: 410–421.

33. AguirreS, MaestreAM, PagniS, PatelJR, SavageT, et al. (2012) DENV inhibits type I IFN production in infected cells by cleaving human STING. PLoS Pathog 8: e1002934.

34. ShrestaS, ShararKL, PrigozhinDM, BeattyPR, HarrisE (2006) A murine model for dengue lethal disease with increased vascular permeability. J Virol 80: 10208–10217.

35. BalsitisSJ, ColomaJ, CastroG, AlavaA, FloresD, et al. (2009) Tropism of dengue virus in mice and humans defined by viral nonstructural protein 3-specific immunostaining. Am J Trop Med Hyg 80: 416–424.

36. OrozcoS, SchmidMA, ParameswaranP, LachicaR, HennMR, et al. (2012) Characterization of a model of lethal dengue virus 2 infection in C57BL/6 mice deficient in the alpha/beta interferon receptor. J Gen Virol 93: 2152–2157.

37. MeradM, GinhouxF, CollinM (2008) Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nat Rev Immunol 8: 935–947.

38. SerbinaNV, Salazar-MatherTP, BironCA, KuzielWA, PamerEG (2003) TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection. Immunity 19: 59–70.

39. NakanoH, LinKL, YanagitaM, CharbonneauC, CookDN, et al. (2009) Blood-derived inflammatory dendritic cells in lymph nodes stimulate acute T helper type 1 immune responses. Nat Immunol 10: 394–402.

40. BogunovicM, GinhouxF, WagersA, LoubeauM, IsolaLM, et al. (2006) Identification of a radio-resistant and cycling dermal dendritic cell population in mice and men. J Exp Med 203: 2627–2638.

41. LibratyDH, PichyangkulS, AjariyakhajornC, EndyTP, EnnisFA (2001) Human dendritic cells are activated by dengue virus infection: enhancement by gamma interferon and implications for disease pathogenesis. Journal of Virology 75: 3501–3508.

42. PalmerDR, SunP, CelluzziC, BisbingJ, PangS, et al. (2005) Differential effects of dengue virus on infected and bystander dendritic cells. J Virol 79: 2432–2439.

43. AderDB, CelluzziC, BisbingJ, GilmoreL, GuntherV, et al. (2004) Modulation of dengue virus infection of dendritic cells by Aedes aegypti saliva. Viral Immunol 17: 252–265.

44. CoxJ, MotaJ, Sukupolvi-PettyS, DiamondMS, Rico-HesseR (2012) Mosquito bite delivery of dengue virus enhances immunogenicity and pathogenesis in humanized mice. J Virol 86: 7637–7649.

45. McCrackenMK, ChristoffersonRC, ChisenhallDM, MoresCN (2014) Analysis of early dengue virus infection in mice as modulated by Aedes aegypti probing. J Virol 88: 1881–1889.

46. Varol C, Vallon-Eberhard A, Elinav E, Aychek T, Shapira Y, et al. (2009) Intestinal Lamina Propria Dendritic Cell Subsets Have Different Origin and Functions. Immunity: 502–512.

47. VarolC, LandsmanL, FoggDK, GreenshteinL, GildorB, et al. (2007) Monocytes give rise to mucosal, but not splenic, conventional dendritic cells. J Exp Med 204: 171–180.

48. EidsmoL, AllanR, CaminschiI, van RooijenN, HeathWR, et al. (2009) Differential migration of epidermal and dermal dendritic cells during skin infection. J Immunol 182: 3165–3172.

49. ReinhartTA (2003) Chemokine induction by HIV-1: recruitment to the cause. Trends Immunol 24: 351–353.

50. SaidiH, MagriG, CarbonneilC, NasreddineN, RequenaM, et al. (2007) IFN-gamma-activated monocytes weakly produce HIV-1 but induce the recruitment of HIV-sensitive T cells and enhance the viral production by these recruited T cells. J Leukoc Biol 81: 642–653.

51. XuH, WangX, VeazeyRS (2013) Mucosal immunology of HIV infection. Immunol Rev 254: 10–33.

52. SerbinaNV, PamerEG (2006) Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol 7: 311–317.

53. Daley-BauerLP, WynnGM, MocarskiES (2012) Cytomegalovirus impairs antiviral CD8+ T cell immunity by recruiting inflammatory monocytes. Immunity 37: 122–133.

54. LeeYR, LiuMT, LeiHY, LiuCC, WuJM, et al. (2006) MCP-1, a highly expressed chemokine in dengue haemorrhagic fever/dengue shock syndrome patients, may cause permeability change, possibly through reduced tight junctions of vascular endothelium cells. J Gen Virol 87: 3623–3630.

55. Le BorgneM, EtchartN, GoubierA, LiraSA, SirardJC, et al. (2006) Dendritic cells rapidly recruited into epithelial tissues via CCR6/CCL20 are responsible for CD8+ T cell crosspriming in vivo. Immunity 24: 191–201.

56. LeeHK, ZamoraM, LinehanMM, IijimaN, GonzalezD, et al. (2009) Differential roles of migratory and resident DCs in T cell priming after mucosal or skin HSV-1 infection. J Exp Med 206: 359–370.

57. Bogunovic M, Ginhoux F, Helft J, Shang L, Hashimoto D, et al. (2009) Origin of the Lamina Propria Dendritic Cell Network. Immunity: 513–525.

58. BoonnakK, SlikeBM, BurgessTH, MasonRM, WuSJ, et al. (2008) Role of dendritic cells in antibody-dependent enhancement of dengue virus infection. J Virol 82: 3939–3951.

59. Navarro-SanchezE, AltmeyerR, AmaraA, SchwartzO, FieschiF, et al. (2003) Dendritic-cell-specific ICAM3-grabbing non-integrin is essential for the productive infection of human dendritic cells by mosquito-cell-derived dengue viruses. EMBO reports 4: 723–729.

60. CheongC, MatosI, ChoiJH, DandamudiDB, ShresthaE, et al. (2010) Microbial stimulation fully differentiates monocytes to DC-SIGN/CD209(+) dendritic cells for immune T cell areas. Cell 143: 416–429.

61. BlackleyS, KouZ, ChenH, QuinnM, RoseRC, 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.

62. AshourJ, Laurent-RolleM, ShiPY, Garcia-SastreA (2009) NS5 of dengue virus mediates STAT2 binding and degradation. J Virol 83: 5408–5418.

63. TanGK, NgJK, TrastiSL, SchulW, YipG, et al. (2010) A non mouse-adapted dengue virus strain as a new model of severe dengue infection in AG129 mice. PLoS Negl Trop Dis 4: e672.

64. PrestwoodTR, MayMM, PlummerEM, MorarMM, YauchLE, et al. (2012) Trafficking and replication patterns reveal splenic macrophages as major targets of dengue virus in mice. J Virol 86: 12138–12147.

65. ZompiS, SantichBH, BeattyPR, HarrisE (2012) Protection from secondary dengue virus infection in a mouse model reveals the role of serotype cross-reactive B and T cells. J Immunol 188: 404–416.

66. FuchsJ, ChuH, O'DayP, PylesR, BourneN, et al. (2014) Investigating the efficacy of monovalent and tetravalent dengue vaccine formulations against DENV-4 challenge in AG129 mice. Vaccine [epub ahead of print] doi:10.1016/j.vaccine.2014.08.087

67. MakhlufH, BuckMD, KingK, PerryST, HennMR, et al. (2013) Tracking the evolution of dengue virus strains D2S10 and D2S20 by 454 pyrosequencing. PLoS ONE 8: e54220.

68. MullerU, SteinhoffU, ReisLF, HemmiS, PavlovicJ, et al. (1994) Functional role of type I and type II interferons in antiviral defense. Science 264: 1918–1921.

69. HelftJ, MeradM (2010) Isolation of cutaneous dendritic cells. Methods Mol Biol 595: 231–233.

70. StoitznerP, RomaniN, McLellanAD, TrippCH, EbnerS (2010) Isolation of skin dendritic cells from mouse and man. Methods Mol Biol 595: 235–248.