Polyfunctional natural killer cells with a low activation profile in response to Toll-like receptor 3 activation in HIV-1-exposed seronegative subjects

Carregando...
Imagem de Miniatura
Citações na Scopus
20
Tipo de produção
article
Data de publicação
2017
Título da Revista
ISSN da Revista
Título do Volume
Editora
NATURE PUBLISHING GROUP
Citação
SCIENTIFIC REPORTS, v.7, article ID 524, 9p, 2017
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Natural killer (NK) cells are the main mediator of the cytotoxic response in innate immunity and may be involved in resistance to HIV-1 infection in exposed seronegative (ESN) individuals. Toll-like receptor (TLR) signalling is crucial for NK cell activation. Here, we investigated the polyfunctional NK cell response to TLR3 activation in serodiscordant couples. ESN subjects showed increased IFN-gamma. and CD107a expression in both NK subsets, CD56(bright) and CD56(dim) cells, in response to stimulation with a TLR3 agonist, while expression was impaired in the HIV-1-infected partners. TLR3-induced expression of IFN-gamma, TNF and CD107a by polyfunctional CD56bright NK cells was more pronounced in ESN individuals than that in healthy controls. Activated NK cells, as determined by CD38 expression, were increased only in the HIV-1-infected partners, with reduced IFN-gamma. and CD107a expression. Moreover, CD38(+) NK cells of the HIV-1-infected partners were associated with increased expression of inhibitory molecules, such as NKG2A, PD- 1 and Tim-3, while NK cells from ESN subjects showed decreased NKG2A expression. Altogether, these findings indicate that NK cells of ESN individuals were highly responsive to TLR3 activation and had a polyfunctional NK cell phenotype, while the impaired TLR3 response in HIV-1-infected partners was associated with an inhibitory/ exhaustion NK cell phenotype.
Palavras-chave
Referências
  1. Arthos J, 2008, NAT IMMUNOL, V9, P301, DOI 10.1038/ni1566
  2. Aujla SJ, 2009, J MOL MED-JMM, V87, P451, DOI 10.1007/s00109-009-0448-1
  3. Begaud E, 2006, RETROVIROLOGY, V3, DOI 10.1186/1742-4690-3-35
  4. Benito JM, 2004, AIDS RES HUM RETROV, V20, P227
  5. Betts MR, 2006, BLOOD, V107, P4781, DOI 10.1182/blood-2005-12-4818
  6. Bixler S. L., 2013, CLIN DEV IMMUNOL, V2013, DOI 10.1155/2013/852418
  7. Brandt L, 2013, JAIDS-J ACQ IMM DEF, V63, P418, DOI 10.1097/QAI.0b013e31828fa22b
  8. Brenchley JM, 2008, BLOOD, V112, P2826, DOI 10.1182/blood-2008-05-159301
  9. Carrillo J, 2013, AIDS, V27, P1375, DOI 10.1097/QAD.0b013e32835fac08
  10. Cicala C, 2009, P NATL ACAD SCI USA, V106, P20877, DOI 10.1073/pnas.0911796106
  11. Clerici M, 2002, AIDS, V16, P1731, DOI 10.1097/00002030-200209060-00004
  12. Deeks SG, 2004, BLOOD, V104, P942, DOI 10.1182/blood-2003-09-3333
  13. Dunkle KL, 2008, LANCET, V371, P2183, DOI 10.1016/S0140-6736(08)60953-8
  14. Erickson AL, 2008, CLIN VACCINE IMMUNOL, V15, P1745, DOI 10.1128/CVI.00247-08
  15. Ferre AL, 2009, BLOOD, V113, P3978, DOI 10.1182/blood-2008-10-182709
  16. Giorgi JV, 2002, J ACQ IMMUN DEF SYND, V29, P346
  17. HO M, 1990, REV INFECT DIS, V12, pS701
  18. Horton RE, 2010, J INFECT DIS, V202, pS377, DOI 10.1086/655971
  19. Hua S, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0101920
  20. Johansson-Lindbom B, 2007, IMMUNOL REV, V215, P226, DOI 10.1111/j.1600-065X.2006.00482.x
  21. Kim CJ, 2013, J IMMUNOL, V191, P2164, DOI 10.4049/jimmunol.1300829
  22. Koning FA, 2005, J IMMUNOL, V175, P6117
  23. Lederman MM, 2010, J INFECT DIS, V202, pS333, DOI 10.1086/655967
  24. Lee J, 2011, MOL CELL BIOL, V31, P3963, DOI 10.1128/MCB.05297-11
  25. Liang SC, 2006, J EXP MED, V203, P2271, DOI 10.1084/jem.20061308
  26. Liu R, 1996, CELL, V86, P367, DOI 10.1016/S0092-8674(00)80110-5
  27. Liu Y, 2011, IMMUNOLOGY, V132, P540, DOI 10.1111/j.1365-2567.2010.03399.x
  28. McLaren PJ, 2010, J INFECT DIS, V202, pS339, DOI 10.1086/655968
  29. Murashev BV, 2012, AIDS RES HUM RETROV, V28, P1598, DOI [10.1089/AID.2011.0335, 10.1089/aid.2011.0335]
  30. Ndhlovu LC, 2012, BLOOD, V119, P3734, DOI 10.1182/blood-2011-11-392951
  31. Pancino G, 2010, J INFECT DIS, V202, pS345, DOI 10.1086/655973
  32. Pera A, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0088538
  33. Ravet S, 2007, BLOOD, V109, P4296, DOI 10.1182/blood-2006-08-040238
  34. Schmidt KN, 2004, J IMMUNOL, V172, P138
  35. Shearer G, 2010, J INFECT DIS, V202, pS329, DOI 10.1086/655974
  36. Sironi M, 2012, J IMMUNOL, V188, P818, DOI 10.4049/jimmunol.1102179
  37. Taborda NA, 2015, AIDS RES HUM RETROV, V31, P636, DOI [10.1089/AID.2014.0325, 10.1089/aid.2014.0325]
  38. Trifari S, 2009, NAT IMMUNOL, V10, P864, DOI 10.1038/ni.1770
  39. UNAIDS, 2013, GLOB REP GLOB AIDS E
  40. Van Braeckel E, 2013, VACCINE, V31, P3739, DOI 10.1016/j.vaccine.2013.05.021
  41. van de Weyer Philipp S, 2006, Biochem Biophys Res Commun, V351, P571, DOI 10.1016/j.bbrc.2006.10.079
  42. Zhang RJ, 2007, AIDS, V21, pS9, DOI 10.1097/01.aids.0000304691.32014.19
  43. Zhu C, 2005, NAT IMMUNOL, V6, P1245, DOI 10.1038/ni1271