HSV-2 Infection of Dendritic Cells Amplifies a Highly Susceptible HIV-1 Cell Target
Herpes simplex virus type 2 (HSV-2) increases the risk of HIV-1 infection and, although several reports describe the interaction between these two viruses, the exact mechanism for this increased susceptibility remains unclear. Dendritic cells (DCs) at the site of entry of HSV-2 and HIV-1 contribute to viral spread in the mucosa. Specialized DCs present in the gut-associated lymphoid tissues produce retinoic acid (RA), an important immunomodulator, able to influence HIV-1 replication and a key mediator of integrin α4β7 on lymphocytes. α4β7 can be engaged by HIV-1 on the cell-surface and CD4+ T cells expressing high levels of this integrin (α4β7high) are particularly susceptible to HIV-1 infection. Herein we provide in-vivo data in macaques showing an increased percentage of α4β7high CD4+ T cells in rectal mucosa, iliac lymph nodes and blood within 6 days of rectal exposure to live (n = 11), but not UV-treated (n = 8), HSV-2. We found that CD11c+ DCs are a major target of HSV-2 infection in in-vitro exposed PBMCs. We determined that immature monocyte-derived DCs (moDCs) express aldehyde dehydrogenase ALDH1A1, an enzyme essential for RA production, which increases upon HSV-2 infection. Moreover, HSV-2-infected moDCs significantly increase α4β7 expression on CD4+ T lymphocytes and HIV-1 infection in DC-T cell mixtures in a RA-dependent manner. Thus, we propose that HSV-2 modulates its microenviroment, influencing DC function, increasing RA production capability and amplifying a α4β7highCD4+ T cells. These factors may play a role in increasing the susceptibility to HIV-1.
Vyšlo v časopise:
HSV-2 Infection of Dendritic Cells Amplifies a Highly Susceptible HIV-1 Cell Target. PLoS Pathog 7(6): e32767. doi:10.1371/journal.ppat.1002109
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1002109
Souhrn
Herpes simplex virus type 2 (HSV-2) increases the risk of HIV-1 infection and, although several reports describe the interaction between these two viruses, the exact mechanism for this increased susceptibility remains unclear. Dendritic cells (DCs) at the site of entry of HSV-2 and HIV-1 contribute to viral spread in the mucosa. Specialized DCs present in the gut-associated lymphoid tissues produce retinoic acid (RA), an important immunomodulator, able to influence HIV-1 replication and a key mediator of integrin α4β7 on lymphocytes. α4β7 can be engaged by HIV-1 on the cell-surface and CD4+ T cells expressing high levels of this integrin (α4β7high) are particularly susceptible to HIV-1 infection. Herein we provide in-vivo data in macaques showing an increased percentage of α4β7high CD4+ T cells in rectal mucosa, iliac lymph nodes and blood within 6 days of rectal exposure to live (n = 11), but not UV-treated (n = 8), HSV-2. We found that CD11c+ DCs are a major target of HSV-2 infection in in-vitro exposed PBMCs. We determined that immature monocyte-derived DCs (moDCs) express aldehyde dehydrogenase ALDH1A1, an enzyme essential for RA production, which increases upon HSV-2 infection. Moreover, HSV-2-infected moDCs significantly increase α4β7 expression on CD4+ T lymphocytes and HIV-1 infection in DC-T cell mixtures in a RA-dependent manner. Thus, we propose that HSV-2 modulates its microenviroment, influencing DC function, increasing RA production capability and amplifying a α4β7highCD4+ T cells. These factors may play a role in increasing the susceptibility to HIV-1.
Zdroje
1. FreemanEEWeissHAGlynnJRCrossPLWhitworthJA 2006 Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS 20 73 83
2. LingappaJRBaetenJMWaldAHughesJPThomasKK 2010 Daily acyclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial. Lancet 375 824 833
3. ZhuJHladikFWoodwardAKlockAPengT 2009 Persistence of HIV-1 receptor-positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition. Nat Med 15 886 892
4. MikloskaZBosnjakLCunninghamAL 2001 Immature monocyte-derived dendritic cells are productively infected with herpes simplex virus type 1. J Virol 75 5958 5964
5. SalioMCellaMSuterMLanzavecchiaA 1999 Inhibition of dendritic cell maturation by herpes simplex virus. Eur J Immunol 29 3245 3253
6. PerettiSShawABlanchardJBohmRMorrowG 2005 Immunomodulatory effects of HSV-2 infection on immature macaque dendritic cells modify innate and adaptive responses. Blood 106 1305 1313
7. de JongMAde WitteLBolmstedtAvan KooykYGeijtenbeekTB 2008 Dendritic cells mediate herpes simplex virus infection and transmission through the C-type lectin DC-SIGN. J Gen Virol 89 2398 2409
8. FruhKAhnKDjaballahHSempePvan EndertPM 1995 A viral inhibitor of peptide transporters for antigen presentation. Nature 375 415 418
9. HillAJugovicPYorkIRussGBenninkJ 1995 Herpes simplex virus turns off the TAP to evade host immunity. Nature 375 411 415
10. CrostarosaFAravantinouMAkpoghenetaOJJasnyEShawA 2009 A macaque model to study vaginal HSV-2/immunodeficiency virus co-infection and the impact of HSV-2 on microbicide efficacy. PLoS ONE 4 e8060
11. ShethPMSunderjiSShinLYRebbapragadaAHuibnerS 2008 Coinfection with herpes simplex virus type 2 is associated with reduced HIV-specific T cell responses and systemic immune activation. J Infect Dis 197 1394 1401
12. IwataMHirakiyamaAEshimaYKagechikaHKatoC 2004 Retinoic acid imprints gut-homing specificity on T cells. Immunity 21 527 538
13. SemmelMMachoACoulaudDAlilecheAPlaisanceS 1994 Effect of retinoic acid on HL-60 cells infected with human immunodeficiency virus type 1. Blood 84 2480 2488
14. PoliGFauciAS 1992 The effect of cytokines and pharmacologic agents on chronic HIV infection. AIDS Res Hum Retroviruses 8 191 197
15. TurpinJAVargoMMeltzerMS 1992 Enhanced HIV-1 replication in retinoid-treated monocytes. Retinoid effects mediated through mechanisms related to cell differentiation and to a direct transcriptional action on viral gene expression. J Immunol 148 2539 2546
16. MackayCR 1991 T-cell memory: the connection between function, phenotype and migration pathways. Immunol Today 12 189 192
17. WagnerNLohlerJKunkelEJLeyKLeungE 1996 Critical role for beta7 integrins in formation of the gut-associated lymphoid tissue. Nature 382 366 370
18. PickerLJ 2006 Immunopathogenesis of acute AIDS virus infection. Curr Opin Immunol 18 399 405
19. AnsariAAReimannKAMayneAETakahashiYStephensonST 2011 Blocking of alpha4beta7 gut-homing integrin during acute infection leads to decreased plasma and gastrointestinal tissue viral loads in simian immunodeficiency virus-infected rhesus macaques. J Immunol 186 1044 1059
20. ArthosJCicalaCMartinelliEMacleodKVan RykD 2008 HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells. Nat Immunol 9 301 309
21. CicalaCMartinelliEMcNallyJPGoodeDJGopaulR 2009 The integrin alpha4beta7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1. Proc Natl Acad Sci U S A 106 20877 20882
22. KaderMBixlerSRoedererMVeazeyRMattapallilJJ 2009 CD4 T cell subsets in the mucosa are CD28+Ki-67-HLA-DR-CD69+ but show differential infection based on alpha4beta7 receptor expression during acute SIV infection. J Med Primatol 38 Suppl 1 24 31
23. NawazFCicalaCVan RykDBlockKEJelicicK 2011 The Genotype of Early-Transmitting HIV gp120s Promotes alpha(4)beta(7) -Reactivity, Revealing alpha(4)beta(7)/CD4 T cells As Key Targets in Mucosal Transmission. PLoS Pathog 7 e1001301
24. HaaseAT 2010 Targeting early infection to prevent HIV-1 mucosal transmission. Nature 464 217 223
25. MoraJR 2008 Homing imprinting and immunomodulation in the gut: role of dendritic cells and retinoids. Inflamm Bowel Dis 14 275 289
26. LampenAMeyerSArnholdTNauH 2000 Metabolism of vitamin A and its active metabolite all-trans-retinoic acid in small intestinal enterocytes. J Pharmacol Exp Ther 295 979 985
27. YoshiokaAOkamotoROshimaSAkiyamaJTsuchiyaK 2008 Flagellin stimulation suppresses IL-7 secretion of intestinal epithelial cells. Cytokine 44 57 64
28. IlievIDSpadoniIMiletiEMatteoliGSonzogniA 2009 Human intestinal epithelial cells promote the differentiation of tolerogenic dendritic cells. Gut 58 1481 1489
29. MolenaarRGreuterMvan der MarelAPRoozendaalRMartinSF 2009 Lymph node stromal cells support dendritic cell-induced gut-homing of T cells. J Immunol 183 6395 6402
30. HammerschmidtSIAhrendtMBodeUWahlBKremmerE 2008 Stromal mesenteric lymph node cells are essential for the generation of gut-homing T cells in vivo. J Exp Med 205 2483 2490
31. GuilliamsMCrozatKHenriSTamoutounourSGrenotP 2010 Skin-draining lymph nodes contain dermis-derived CD103(−) dendritic cells that constitutively produce retinoic acid and induce Foxp3(+) regulatory T cells. Blood 115 1958 1968
32. YokotaATakeuchiHMaedaNOhokaYKatoC 2009 GM-CSF and IL-4 synergistically trigger dendritic cells to acquire retinoic acid-producing capacity. Int Immunol 21 361 377
33. ManicassamySRavindranRDengJOluochHDenningTL 2009 Toll-like receptor 2-dependent induction of vitamin A-metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoimmunity. Nat Med 15 401 409
34. JonesCAFernandezMHercKBosnjakLMiranda-SaksenaM 2003 Herpes simplex virus type 2 induces rapid cell death and functional impairment of murine dendritic cells in vitro. J Virol 77 11139 11149
35. PerfettoSPChattopadhyayPKLamoreauxLNguyenRAmbrozakD 2006 Amine reactive dyes: an effective tool to discriminate live and dead cells in polychromatic flow cytometry. J Immunol Methods 313 199 208
36. AubertMYoonMSloanDDSpearPGJeromeKR 2009 The virological synapse facilitates herpes simplex virus entry into T cells. J Virol 83 6171 6183
37. KeidelSLeMottePApfelC 1994 Different agonist- and antagonist-induced conformational changes in retinoic acid receptors analyzed by protease mapping. Mol Cell Biol 14 287 298
38. DenucciCCMitchellJSShimizuY 2009 Integrin function in T-cell homing to lymphoid and nonlymphoid sites: getting there and staying there. Crit Rev Immunol 29 87 109
39. KellyKANatarajanSRutherPWisseAChangMH 2001 Chlamydia trachomatis infection induces mucosal addressin cell adhesion molecule-1 and vascular cell adhesion molecule-1, providing an immunologic link between the fallopian tube and other mucosal tissues. J Infect Dis 184 885 891
40. KellyKAWileyDWiesmeierEBriskinMButchA 2009 The combination of the gastrointestinal integrin (alpha4beta7) and selectin ligand enhances T-Cell migration to the reproductive tract during infection with Chlamydia trachomatis. Am J Reprod Immunol 61 446 452
41. GrantAJLalorPFHubscherSGBriskinMAdamsDH 2001 MAdCAM-1 expressed in chronic inflammatory liver disease supports mucosal lymphocyte adhesion to hepatic endothelium (MAdCAM-1 in chronic inflammatory liver disease). Hepatology 33 1065 1072
42. SoderbergKALinehanMMRuddleNHIwasakiA 2004 MAdCAM-1 expressing sacral lymph node in the lymphotoxin beta-deficient mouse provides a site for immune generation following vaginal herpes simplex virus-2 infection. J Immunol 173 1908 1913
43. IwasakiAKelsallBL 1999 Mucosal immunity and inflammation. I. Mucosal dendritic cells: their specialized role in initiating T cell responses. Am J Physiol 276 G1074 1078
44. LeeHKZamoraMLinehanMMIijimaNGonzalezD 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
45. KassimSHRajasagiNKZhaoXChervenakRJenningsSR 2006 In vivo ablation of CD11c-positive dendritic cells increases susceptibility to herpes simplex virus type 1 infection and diminishes NK and T-cell responses. J Virol 80 3985 3993
46. SteinmanRMHawigerDNussenzweigMC 2003 Tolerogenic dendritic cells. Annu Rev Immunol 21 685 711
47. LundJMLinehanMMIijimaNIwasakiA 2006 Cutting Edge: Plasmacytoid dendritic cells provide innate immune protection against mucosal viral infection in situ. J Immunol 177 7510 7514
48. DonaghyHBosnjakLHarmanANMarsdenVTyringSK 2009 Role for plasmacytoid dendritic cells in the immune control of recurrent human herpes simplex virus infection. J Virol 83 1952 1961
49. SalioMCellaMSuterMLanzavecchiaA 1999 Inhibition of dendritic cell maturation by herpes simplex virus. Eur J Immunol 29 3245 3253
50. BosnjakLMiranda-SaksenaMKoelleDMBoadleRAJonesCA 2005 Herpes Simplex Virus Infection of Human Dendritic Cells Induces Apoptosis and Allows Cross-Presentation via Uninfected Dendritic Cells. J Immunol 174 2220 2227
51. SaurerLMcCulloughKCSummerfieldA 2007 In vitro induction of mucosa-type dendritic cells by all-trans retinoic acid. J Immunol 179 3504 3514
52. YamaguchiKGroopmanJEByrnRA 1994 The regulation of HIV by retinoic acid correlates with cellular expression of the retinoic acid receptors. AIDS 8 1675 1682
53. UittenbogaartCHBoscardinWJAnisman-PosnerDJKokaPSBristolG 2000 Effect of cytokines on HIV-induced depletion of thymocytes in vivo. AIDS 14 1317 1325
54. WangFXXuYSullivanJSouderEArgyrisEG 2005 IL-7 is a potent and proviral strain-specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART. J Clin Invest 115 128 137
55. MelchjorsenJSirenJJulkunenIPaludanSRMatikainenS 2006 Induction of cytokine expression by herpes simplex virus in human monocyte-derived macrophages and dendritic cells is dependent on virus replication and is counteracted by ICP27 targeting NF-kappaB and IRF-3. J Gen Virol 87 1099 1108
56. AbelKLa Franco-ScheuchLRourkeTMaZMDe SilvaV 2004 Gamma interferon-mediated inflammation is associated with lack of protection from intravaginal simian immunodeficiency virus SIVmac239 challenge in simian-human immunodeficiency virus 89.6-immunized rhesus macaques. J Virol 78 841 854
57. AurelianL 2000 Herpes Simplex Virus. SpecterSHRYoungSA Clinical Virology Manual. 3rd ed Washington, DC ASM Press 384 409
58. DouekDCBrenchleyJMBettsMRAmbrozakDRHillBJ 2002 HIV preferentially infects HIV-specific CD4+ T cells. Nature 417 95 98
59. RozenSSkaletskyH 2000 Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 132 365 386
60. FrankIPiatakMJrStoesselHRomaniNBonnyayD 2002 Infectious and whole inactivated simian immunodeficiency viruses interact similarly with primate dendritic cells (DCs): differential intracellular fate of virions in mature and immature DCs. J Virol 76 2936 2951
61. ClineANBessJWPiatakMJrLifsonJD 2005 Highly sensitive SIV plasma viral load assay: practical considerations, realistic performance expectations, and application to reverse engineering of vaccines for AIDS. J Med Primatol 34 303 312
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2011 Číslo 6
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
Najčítanejšie v tomto čísle
- High Affinity Nanobodies against the VSG Are Potent Trypanolytic Agents that Block Endocytosis
- Structural and Mechanistic Studies of Measles Virus Illuminate Paramyxovirus Entry
- Sporangiospore Size Dimorphism Is Linked to Virulence of
- The Binding of Triclosan to SmeT, the Repressor of the Multidrug Efflux Pump SmeDEF, Induces Antibiotic Resistance in