1887

Journal of General Virology header logo

Volume 98, Issue 3

CCR6/CCL20 chemokine axis in human immunodeficiency virus immunity and pathogenesis Free

Abstract

Recent studies in human immunodeficiency virus (HIV) have garnered interest for the role of CC chemokine receptor 6 (CCR6) and its known ligands, CC chemokine ligand 20 (CCL20) and human β-defensins, in viral entry, dissemination and antiviral immunity. Several studies have suggested that CCR6 may also act as a weak co-receptor of HIV entry, in addition to the canonical CXC chemokine receptor 4 (CXCR4) and CCR5. However, the pathogenic significance has yet to be demonstrated as the observations for preferential infection of CD4CCR6 over CD4CCR6 T cells appear to be independent of CCR6 expression. This indicates means for preferential infection other than CCR6 co-receptor use. Attention has also turned to the inadvertent role of the CCR6/CCL20 axis in attracting key immune cells, including T17 cells and dendritic cells, to sites of infection and propagating the virus to other sites of the body. This review article will summarize the latest evidence that the CCR6/CCL20 chemokine axis is playing an important role in HIV pathogenesis and immunity. Further work with studies is needed to establish the biological and, hence, therapeutic significance of these findings.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): CCL20 , CCR6 , chemokines , co-receptors and HIV
© 2017 The Authors
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000691
2017-03-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/98/3/338.html?itemId=/content/journal/jgv/10.1099/jgv.0.000691&mimeType=html&fmt=ahah

References

  1. Shimizu N, Tanaka A, Oue A, Mori T, Ohtsuki T et al. Broad usage spectrum of G protein-coupled receptors as coreceptors by primary isolates of HIV. AIDS 2009; 23:761–769 [View Article][PubMed]
     [Google Scholar]
  2. Nedellec R, Coetzer M, Shimizu N, Hoshino H, Polonis VR et al. Virus entry via the alternative coreceptors CCR3 and FPRL1 differs by human immunodeficiency virus type 1 subtype. J Virol 2009; 83:8353–8363 [View Article][PubMed]
     [Google Scholar]
  3. Schutyser E, Struyf S, Van Damme J. The CC chemokine CCL20 and its receptor CCR6. Cytokine Growth Factor Rev 2003; 14:409–426 [View Article][PubMed]
     [Google Scholar]
  4. Lee AYS, Eri R, Lyons AB, Grimm MC, Korner H. CC chemokine ligand 20 and its cognate receptor CCR6 in mucosal T cell immunology and inflammatory bowel disease: odd couple or axis of evil?. Front Immunol 2013; 4:194 [View Article][PubMed]
     [Google Scholar]
  5. Baba M, Imai T, Nishimura M, Kakizaki M, Takagi S et al. Identification of CCR6, the specific receptor for a novel lymphocyte-directed CC chemokine LARC. J Biol Chem 1997; 272:14893–14898 [View Article][PubMed]
     [Google Scholar]
  6. Mcgeachy MJ. Th17 memory cells: live long and proliferate. J Leukoc Biol 2013; 94:921–926 [View Article][PubMed]
     [Google Scholar]
  7. Berahovich RD, Lai NL, Wei Z, Lanier LL, Schall TJ. Evidence for NK cell subsets based on chemokine receptor expression. J Immunol 2006; 177:7833–7840 [View Article][PubMed]
     [Google Scholar]
  8. Gray EE, Suzuki K, Cyster JG. Cutting edge: identification of a motile IL-17-producing γδ T cell population in the dermis. J Immunol 2011; 186:6091–6095 [View Article][PubMed]
     [Google Scholar]
  9. Cook DN, Prosser DM, Forster R, Zhang J, Kuklin NA et al. CCR6 mediates dendritic cell localization, lymphocyte homeostasis, and immune responses in mucosal tissue. Immunity 2000; 12:495–503 [View Article][PubMed]
     [Google Scholar]
  10. Varona R, Villares R, Carramolino L, Goya I, Zaballos A et al. CCR6-deficient mice have impaired leukocyte homeostasis and altered contact hypersensitivity and delayed-type hypersensitivity responses. J Clin Invest 2001; 107:R37–R45 [View Article][PubMed]
     [Google Scholar]
  11. Lügering A, Floer M, Westphal S, Maaser C, Spahn TW et al. Absence of CCR6 inhibits CD4+ regulatory T-cell development and M-cell formation inside Peyer's patches. Am J Pathol 2005; 166:1647–1654 [View Article][PubMed]
     [Google Scholar]
  12. Elgueta R, Marks E, Nowak E, Menezes S, Benson M et al. CCR6-dependent positioning of memory B cells is essential for their ability to mount a recall response to antigen. J Immunol 2015; 194:505–513 [View Article][PubMed]
     [Google Scholar]
  13. Reimer D, Lee AY, Bannan J, Fromm P, Kara EE et al. Early CCR6 expression on B cells modulates germinal centre kinetics and efficient antibody responses. Immunol Cell Biol 2017; 95:33–41 [View Article][PubMed]
     [Google Scholar]
  14. Wiede F, Fromm PD, Comerford I, Kara E, Bannan J et al. CCR6 is transiently upregulated on B cells after activation and modulates the germinal center reaction in the mouse. Immunol Cell Biol 2013; 91:335–339 [View Article][PubMed]
     [Google Scholar]
  15. Lee AYS, Phan TK, Hulett MD, Körner H. The relationship between CCR6 and its binding partners: does the CCR6–CCL20 axis have to be extended?. Cytokine 2015; 72:97–101 [View Article][PubMed]
     [Google Scholar]
  16. Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ et al. β-Defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 1999; 286:525–528 [View Article][PubMed]
     [Google Scholar]
  17. Wilen CB, Tilton JC, Doms RW. HIV: cell binding and entry. Cold Spring Harb Perspect Med 2012; 2:a006866 [View Article][PubMed]
     [Google Scholar]
  18. Gorry PR, Ancuta P. Coreceptors and HIV-1 pathogenesis. Curr HIV/AIDS Rep 2011; 8:45–53 [View Article][PubMed]
     [Google Scholar]
  19. Islam S, Shimizu N, Hoque SA, Jinno-Oue A, Tanaka A et al. CCR6 functions as a new coreceptor for limited primary human and simian immunodeficiency viruses. PLoS One 2013; 8:e73116 [View Article][PubMed]
     [Google Scholar]
  20. Islam S, Kanbe K, Shimizu N, Ohtsuki T, Jinno-Oue A et al. CKR-L3, a deletion version CCR6-isoform shows coreceptor-activity for limited human and simian immunodeficiency viruses. BMC Infect Dis 2014; 14:354 [View Article][PubMed]
     [Google Scholar]
  21. Doranz BJ, Lu ZH, Rucker J, Zhang TY, Sharron M et al. Two distinct CCR5 domains can mediate coreceptor usage by human immunodeficiency virus type 1. J Virol 1997; 71:6305–6314[PubMed]
     [Google Scholar]
  22. Wu Y, Yoder A. Chemokine coreceptor signaling in HIV-1 infection and pathogenesis. PLoS Pathog 2009; 5:e1000520 [View Article][PubMed]
     [Google Scholar]
  23. Kuhmann SE, Platt EJ, Kozak SL, Kabat D. Polymorphisms in the CCR5 genes of African green monkeys and mice implicate specific amino acids in infections by simian and human immunodeficiency viruses. J Virol 1997; 71:8642–8656[PubMed]
     [Google Scholar]
  24. Navenot JM, Wang ZX, Trent JO, Murray JL, Hu QX et al. Molecular anatomy of CCR5 engagement by physiologic and viral chemokines and HIV-1 envelope glycoproteins: differences in primary structural requirements for RANTES, MIP-1α, and vMIP-II binding. J Mol Biol 2001; 313:1181–1193 [View Article][PubMed]
     [Google Scholar]
  25. Ai LS, Lee SF, Chen SS, Liao F. Molecular characterization of CCR6: involvement of multiple domains in ligand binding and receptor signaling. J Biomed Sci 2004; 11:818–828 [View Article][PubMed]
     [Google Scholar]
  26. Efremov R, Truong MJ, Darcissac EC, Zeng J, Grau O et al. Human chemokine receptors CCR5, CCR3 and CCR2B share common polarity motif in the first extracellular loop with other human G-protein coupled receptors: implications for HIV-1 coreceptor function. Eur J Biochem 1999; 263:746–756 [View Article][PubMed]
     [Google Scholar]
  27. Olson WC, Rabut GE, Nagashima KA, Tran DN, Anselma DJ et al. Differential inhibition of human immunodeficiency virus type 1 fusion, gp120 binding, and CC-chemokine activity by monoclonal antibodies to CCR5. J Virol 1999; 73:4145–4155[PubMed]
     [Google Scholar]
  28. Zhang L, Yu W, He T, Yu J, Caffrey RE et al. Contribution of human alpha-defensin 1, 2, and 3 to the anti-HIV-1 activity of CD8 antiviral factor. Science 2002; 298:995–1000 [View Article][PubMed]
     [Google Scholar]
  29. Sun L, Finnegan CM, Kish-Catalone T, Blumenthal R, Garzino-Demo P et al. Human β-defensins suppress human immunodeficiency virus infection: potential role in mucosal protection. J Virol 2005; 79:14318–14329 [View Article][PubMed]
     [Google Scholar]
  30. Herrera R, Morris M, Rosbe K, Feng Z, Weinberg A et al. Human beta-defensins 2 and -3 cointernalize with human immunodeficiency virus via heparan sulfate proteoglycans and reduce infectivity of intracellular virions in tonsil epithelial cells. Virology 2016; 487:172–187 [View Article][PubMed]
     [Google Scholar]
  31. Mohan T, Sharma C, Bhat AA, Rao DN. Modulation of HIV peptide antigen specific cellular immune response by synthetic α- and β-defensin peptides. Vaccine 2013; 31:1707–1716 [View Article][PubMed]
     [Google Scholar]
  32. Lafferty MK, Sun L, Demasi L, Lu W, Garzino-Demo A. CCR6 ligands inhibit HIV by inducing APOBEC3G. Blood 2010; 115:1564–1571 [View Article][PubMed]
     [Google Scholar]
  33. Hardwick RJ, Amogne W, Mugusi S, Yimer G, Ngaimisi E et al. β-Defensin genomic copy number is associated with HIV load and immune reconstitution in sub-saharan Africans. J Infect Dis 2012; 206:1012–1019 [View Article][PubMed]
     [Google Scholar]
  34. Singh SP, Zhang HH, Foley JF, Hedrick MN, Farber JM. Human T cells that are able to produce IL-17 express the chemokine receptor CCR6. J Immunol 2008; 180:214–221 [View Article][PubMed]
     [Google Scholar]
  35. Gosselin A, Monteiro P, Chomont N, Diaz-Griffero F, Said EA et al. Peripheral blood CCR4+CCR6+ and CXCR3+CCR6+CD4+ T cells are highly permissive to HIV-1 infection. J Immunol 2010; 184:1604–1616 [View Article][PubMed]
     [Google Scholar]
  36. Stieh DJ, Matias E, Xu H, Fought AJ, Blanchard JL et al. Th17 cells are preferentially infected very early after vaginal transmission of SIV in macaques. Cell Host Microbe 2016; 19:529–540 [View Article][PubMed]
     [Google Scholar]
  37. Khoury G, Anderson JL, Fromentin R, Hartogenesis W, Smith MZ et al. Persistence of integrated HIV DNA in CXCR3 + CCR6 + memory CD4+ T cells in HIV-infected individuals on antiretroviral therapy. AIDS 2016; 30:1511–1520 [View Article][PubMed]
     [Google Scholar]
  38. Alvarez Y, Tuen M, Shen G, Nawaz F, Arthos J et al. Preferential HIV infection of CCR6+ Th17 cells is associated with higher levels of virus receptor expression and lack of CCR5 ligands. J Virol 2013; 87:10843–10854 [View Article][PubMed]
     [Google Scholar]
  39. Paris RM, Petrovas C, Ferrando-Martinez S, Moysi E, Boswell KL et al. Selective loss of early differentiated, highly functional PD1high CD4 T cells with HIV progression. PLoS One 2015; 10:e0144767 [View Article][PubMed]
     [Google Scholar]
  40. Monteiro P, Gosselin A, Wacleche VS, El-Far M, Said EA et al. Memory CCR6+CD4+ T cells are preferential targets for productive HIV type 1 infection regardless of their expression of integrin β7. J Immunol 2011; 186:4618–4630 [View Article][PubMed]
     [Google Scholar]
  41. Cleret-Buhot A, Zhang Y, Planas D, Goulet JP, Monteiro P et al. Identification of novel HIV-1 dependency factors in primary CCR4+CCR6+Th17 cells via a genome-wide transcriptional approach. Retrovirology 2015; 12:102 [View Article][PubMed]
     [Google Scholar]
  42. Brenchley JM, Paiardini M, Knox KS, Asher AI, Cervasi B et al. Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood 2008; 112:2826–2835 [View Article][PubMed]
     [Google Scholar]
  43. Loiseau C, Requena M, Mavigner M, Cazabat M, Carrere N et al. CCR6− regulatory T cells blunt the restoration of gut Th17 cells along the CCR6–CCL20 axis in treated HIV-1-infected individuals. Mucosal Immunol 2016; 9:1137–1150 [View Article][PubMed]
     [Google Scholar]
  44. El Hed A, Khaitan A, Kozhaya L, Manel N, Daskalakis D et al. Susceptibility of human Th17 cells to human immunodeficiency virus and their perturbation during infection. J Infect Dis 2010; 201:843–854 [View Article][PubMed]
     [Google Scholar]
  45. Guillot-Delost M, Le Gouvello S, Mesel-Lemoine M, Cheraï M, Baillou C et al. Human CD90 identifies Th17/Tc17 T cell subsets that are depleted in HIV-infected patients. J Immunol 2012; 188:981–991 [View Article][PubMed]
     [Google Scholar]
  46. Lécureuil C, Combadière B, Mazoyer E, Bonduelle O, Samri A et al. Trapping and apoptosis of novel subsets of memory T lymphocytes expressing CCR6 in the spleen of HIV-infected patients. Blood 2007; 109:3649–3657 [View Article][PubMed]
     [Google Scholar]
  47. Prendergast A, Prado JG, Kang YH, Chen F, Riddell LA et al. HIV-1 infection is characterized by profound depletion of CD161+ Th17 cells and gradual decline in regulatory T cells. AIDS 2010; 24:491–502 [View Article][PubMed]
     [Google Scholar]
  48. Dafonseca S, Niessl J, Pouvreau S, Wacleche VS, Gosselin A et al. Impaired Th17 polarization of phenotypically naive CD4+ T-cells during chronic HIV-1 infection and potential restoration with early ART. Retrovirology 2015; 12:38 [View Article][PubMed]
     [Google Scholar]
  49. Micci L, Cervasi B, Ende ZS, Iriele RI, Reyes-Aviles E et al. Paucity of IL-21-producing CD4+ T cells is associated with Th17 cell depletion in SIV infection of rhesus macaques. Blood 2012; 120:3925–3935 [View Article][PubMed]
     [Google Scholar]
  50. Takeshita M, Suzuki K, Kassai Y, Takiguchi M, Nakayama Y et al. Polarization diversity of human CD4+ stem cell memory T cells. Clin Immunol 2015; 159:107–117 [View Article][PubMed]
     [Google Scholar]
  51. Mercer F, Khaitan A, Kozhaya L, Aberg JA, Unutmaz D. Differentiation of IL-17-producing effector and regulatory human T cells from lineage-committed naive precursors. J Immunol 2014; 193:1047–1054 [View Article][PubMed]
     [Google Scholar]
  52. Wacleche VS, Goulet JP, Gosselin A, Monteiro P, Soudeyns H et al. New insights into the heterogeneity of Th17 subsets contributing to HIV-1 persistence during antiretroviral therapy. Retrovirology 2016; 13:59 [View Article][PubMed]
     [Google Scholar]
  53. Boswell KL, Paris R, Boritz E, Ambrozak D, Yamamoto T et al. Loss of circulating CD4 T cells with B cell helper function during chronic HIV infection. PLoS Pathog 2014; 10:e1003853 [View Article][PubMed]
     [Google Scholar]
  54. Velu V, Mylvaganam GH, Gangadhara S, Hong JJ, Iyer SS et al. Induction of Th1-biased T follicular helper (Tfh) cells in lymphoid tissues during chronic simian immunodeficiency virus infection defines functionally distinct germinal center Tfh cells. J Immunol 2016; 197:1832–1842 [View Article][PubMed]
     [Google Scholar]
  55. Badr G, Borhis G, Treton D, Moog C, Garraud O et al. HIV type 1 glycoprotein 120 inhibits human B cell chemotaxis to CXC chemokine ligand (CXCL) 12, CC chemokine ligand (CCL)20, and CCL21. J Immunol 2005; 175:302–310 [View Article][PubMed]
     [Google Scholar]
  56. Saeidi A, Tien Tien VL, Al-Batran R, Al-Darraji HA, Tan HY et al. Attrition of TCR vα7.2+ CD161++ MAIT cells in HIV-tuberculosis co-infection is associated with elevated levels of PD-1 expression. PLoS One 2015; 10:e0124659 [View Article][PubMed]
     [Google Scholar]
  57. Wong EB, Akilimali NA, Govender P, Sullivan ZA, Cosgrove C et al. Low levels of peripheral CD161++CD8+ mucosal associated invariant T (MAIT) cells are found in HIV and HIV/TB co-infection. PLoS One 2013; 8:e83474 [View Article][PubMed]
     [Google Scholar]
  58. Manches O, Frleta D, Bhardwaj N. Dendritic cells in progression and pathology of HIV infection. Trends Immunol 2014; 35:114–122 [View Article][PubMed]
     [Google Scholar]
  59. Greaves DR, Wang W, Dairaghi DJ, Dieu MC, Saint-Vis B et al. CCR6, a CC chemokine receptor that interacts with macrophage inflammatory protein 3α and is highly expressed in human dendritic cells. J Exp Med 1997; 186:837–844 [View Article][PubMed]
     [Google Scholar]
  60. Li Q, Estes JD, Schlievert PM, Duan L, Brosnahan AJ et al. Glycerol monolaurate prevents mucosal SIV transmission. Nature 2009; 458:1034–1038 [View Article][PubMed]
     [Google Scholar]
  61. Fontaine J, Poudrier J, Roger M. Short communication: persistence of high blood levels of the chemokines CCL2, CCL19, and CCL20 during the course of HIV infection. AIDS Res Hum Retroviruses 2011; 27:655–657 [View Article][PubMed]
     [Google Scholar]
  62. Donaghy H, Pozniak A, Gazzard B, Qazi N, Gilmour J 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 [View Article][PubMed]
     [Google Scholar]
  63. Choi YK, Fallert BA, Murphey-Corb MA, Reinhart TA. Simian immunodeficiency virus dramatically alters expression of homeostatic chemokines and dendritic cell markers during infection in vivo. Blood 2003; 101:1684–1691 [View Article][PubMed]
     [Google Scholar]
  64. Dieu MC, Vanbervliet B, Vicari A, Bridon JM, Oldham E et al. Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites. J Exp Med 1998; 188:373–386 [View Article][PubMed]
     [Google Scholar]
  65. Lourenço AG, Komesu MC, Machado AA, Quintana SM, Bourlet T et al. Semen lactoferrin promotes CCL20 production by epithelial cells: involvement in HIV transmission. World J Virol 2014; 3:11–17 [View Article][PubMed]
     [Google Scholar]
  66. Berlier W, Cremel M, Hamzeh H, Lévy R, Lucht F et al. Seminal plasma promotes the attraction of Langerhans cells via the secretion of CCL20 by vaginal epithelial cells: involvement in the sexual transmission of HIV. Hum Reprod 2006; 21:1135–1142 [View Article][PubMed]
     [Google Scholar]
  67. Cameron PU, Saleh S, Sallmann G, Solomon A, Wightman F et al. Establishment of HIV-1 latency in resting CD4+ T cells depends on chemokine-induced changes in the actin cytoskeleton. Proc Natl Acad Sci USA 2010; 107:16934–16939 [View Article][PubMed]
     [Google Scholar]
  68. Saleh S, Solomon A, Wightman F, Xhilaga M, Cameron PU et al. CCR7 ligands CCL19 and CCL21 increase permissiveness of resting memory CD4+ T cells to HIV-1 infection: a novel model of HIV-1 latency. Blood 2007; 110:4161–4164 [View Article][PubMed]
     [Google Scholar]
  69. Yang D, Chen Q, Hoover DM, Staley P, Tucker KD et al. Many chemokines including CCL20/MIP-3α display antimicrobial activity. J Leukoc Biol 2003; 74:448–455 [View Article][PubMed]
     [Google Scholar]
  70. Ghosh M, Shen Z, Schaefer TM, Fahey JV, Gupta P et al. CCL20/MIP3α is a novel anti-HIV-1 molecule of the human female reproductive tract. Am J Reprod Immunol 2009; 62:60–71 [View Article][PubMed]
     [Google Scholar]
  71. Moore JP, Kitchen SG, Pugach P, Zack JA. The CCR5 and CXCR4 coreceptors—central to understanding the transmission and pathogenesis of human immunodeficiency virus type 1 infection. AIDS Res Hum Retroviruses 2004; 20:111–126 [View Article][PubMed]
     [Google Scholar]
  72. Coetzer M, Nedellec R, Cilliers T, Meyers T, Morris L et al. Extreme genetic divergence is required for coreceptor switching in HIV-1 subtype C. J Acquir Immune Defic Syndr 2011; 56:9–15 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000691
Loading
CCR6/CCL20 chemokine axis in human immunodeficiency virus immunity and pathogenesis
J. Gen. Virol. 98, 338 (2017); https://doi.org/10.1099/jgv.0.000691
/content/journal/jgv/10.1099/jgv.0.000691
/content/journal/jgv/10.1099/jgv.0.000691
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error