Experimental Hematology
Volume 37, Issue 9 , Pages 1022-1029 , September 2009

Polymorphisms in Toll-like receptor genes and susceptibility to infections in allogeneic stem cell transplantation

  • Agostinho Carvalho

      Affiliations

    • Microbiology, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
    • Corresponding Author InformationOffprint requests to: Agostinho Carvalho, Ph.D., Department of Experimental Medicine and Biochemical Sciences and Ospedale Santa Maria della Misericordia, Microbiology Section, Perugia 06123, Italy
  • ,
  • Cristina Cunha

      Affiliations

    • Microbiology, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
  • ,
  • Alessandra Carotti

      Affiliations

    • Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
  • ,
  • Teresa Aloisi

      Affiliations

    • Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
  • ,
  • Ornella Guarrera

      Affiliations

    • Microbiology, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
  • ,
  • Mauro Di Ianni

      Affiliations

    • Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
  • ,
  • Franca Falzetti

      Affiliations

    • Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
  • ,
  • Francesco Bistoni

      Affiliations

    • Microbiology, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
  • ,
  • Franco Aversa

      Affiliations

    • Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
  • ,
  • Lucia Pitzurra

      Affiliations

    • Microbiology, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
  • ,
  • Fernando Rodrigues

      Affiliations

    • Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal
  • ,
  • Luigina Romani

      Affiliations

    • Microbiology, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy

Received 5 May 2008 ,Revised 29 April 2009 ,Accepted 9 June 2009.

References 

  1. Welniak LA, Blazar BR, Murphy WJ. Immunobiology of allogeneic hematopoietic stem cell transplantation. Annu Rev Immunol. 2007;25:139–170
  2. Cappellano P, Viscoli C, Bruzzi P, Van Lint MT, Pereira CA, Bacigalupo A. Epidemiology and risk factors for bloodstream infections after allogeneic hematopoietic stem cell transplantation. New Microbiol. 2007;30:89–99
  3. Pagano L, Caira M, Nosari A, et al. Fungal infections in recipients of hematopoietic stem cell transplants: results of the SEIFEM B-2004 study—Sorveglianza Epidemiologica Infezioni Fungine Nelle Emopatie Maligne. Clin Infect Dis. 2007;45:1161–1170
  4. Bogunia-Kubik K, Wysoczanska B, Lange A. Non-HLA gene polymorphisms and the outcome of allogeneic hematopoietic stem cell transplantation. Curr Stem Cell Res Ther. 2006;1:239–253
  5. Chen L, Wang T, Zhou P, et al. TLR engagement prevents transplantation tolerance. Am J Transplant. 2006;6:2282–2291
  6. Mayor NP, Shaw BE, Hughes DA, et al. Single nucleotide polymorphisms in the NOD2/CARD15 gene are associated with an increased risk of relapse and death for patients with acute leukemia after hematopoietic stem-cell transplantation with unrelated donors. J Clin Oncol. 2007;25:4262–4269
  7. Schroder NW, Schumann RR. Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease. Lancet Infect Dis. 2005;5:156–164
  8. Schwartz DA, Cook DN. Polymorphisms of the Toll-like receptors and human disease. Clin Infect Dis. 2005;41(Suppl 7):S403–S407
  9. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783–801
  10. Lasker MV, Nair SK. Intracellular TLR signaling: a structural perspective on human disease. J Immunol. 2006;177:11–16
  11. Lazarus R, Vercelli D, Palmer LJ, et al. Single nucleotide polymorphisms in innate immunity genes: abundant variation and potential role in complex human disease. Immunol Rev. 2002;190:9–25
  12. Texereau J, Chiche JD, Taylor W, Choukroun G, Comba B, Mira JP. The importance of Toll-like receptor 2 polymorphisms in severe infections. Clin Infect Dis. 2005;41(Suppl 7):S408–S415
  13. Krieg AM. Therapeutic potential of Toll-like receptor 9 activation. Nat Rev Drug Discov. 2006;5:471–484
  14. Vollmer J. TLR9 in health and disease. Int Rev Immunol. 2006;25:155–181
  15. Lazarus R, Klimecki WT, Raby BA, et al. Single-nucleotide polymorphisms in the Toll-like receptor 9 gene (TLR9): frequencies, pairwise linkage disequilibrium, and haplotypes in three US ethnic groups and exploratory case-control disease association studies. Genomics. 2003;81:85–91
  16. Torok HP, Glas J, Tonenchi L, Bruennler G, Folwaczny M, Folwaczny C. Crohn's disease is associated with a toll-like receptor-9 polymorphism. Gastroenterology. 2004;127:365–366
  17. Lorenz E, Schwartz DA, Martin PJ, et al. Association of TLR4 mutations and the risk for acute GVHD after HLA-matched-sibling hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2001;7:384–387
  18. Arbour NC, Lorenz E, Schutte BC, et al. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet. 2000;25:187–191
  19. Michel O, LeVan TD, Stern D, et al. Systemic responsiveness to lipopolysaccharide and polymorphisms in the toll-like receptor 4 gene in human beings. J Allergy Clin Immunol. 2003;112:923–929
  20. Li H, Sun B. Toll-like receptor 4 in atherosclerosis. J Cell Mol Med. 2007;11:88–95
  21. Ferwerda B, McCall MB, Alonso S, et al. TLR4 polymorphisms, infectious diseases, and evolutionary pressure during migration of modern humans. Proc Natl Acad Sci U S A. 2007;104:16645–16650
  22. Romani L. Immunity to fungal infections. Nat Rev Immunol. 2004;4:1–23
  23. Morre SA, Murillo LS, Spaargaren J, Fennema HS, Pena AS. Role of the toll-like receptor 4 Asp299Gly polymorphism in susceptibility to Candida albicans infection. J Infect Dis. 2002;186:1377–1379author reply 9
  24. Van der Graaf CA, Netea MG, Morre SA, et al. Toll-like receptor 4 Asp299Gly/Thr399Ile polymorphisms are a risk factor for Candida bloodstream infection. Eur Cytokine Netw. 2006;17:29–34
  25. Kesh S, Mensah NY, Peterlongo P, et al. TLR1 and TLR6 polymorphisms are associated with susceptibility to invasive aspergillosis after allogeneic stem cell transplantation. Ann N Y Acad Sci. 2005;1062:95–103
  26. Bochud PY, Chien JW, Marr KA, et al. Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation. N Engl J Med. 2008;359:1766–1777
  27. Land WG. Innate immunity-mediated allograft rejection and strategies to prevent it. Transplant Proc. 2007;39:667–672
  28. Carvalho A, Marques A, Maciel P, Rodrigues F. Study of disease-relevant polymorphisms in the TLR4 and TLR9 genes: A novel method applied to the analysis of the Portuguese population. Mol Cell Probes. 2007;21:316–320
  29. Carvalho A, Pasqualotto AC, Pitzurra L, Romani L, Denning DW, Rodrigues F. Polymorphisms in Toll-like receptor genes and susceptibility to pulmonary aspergillosis. J Infect Dis. 2008;197:618–621
  30. Aversa F, Tabilio A, Velardi A, et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med. 1998;339:1186–1193
  31. Aversa F, Terenzi A, Tabilio A, et al. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol. 2005;23:3447–3454
  32. Tabilio A, Falzetti F, Giannoni C, et al. Stem cell mobilization in normal donors. J Hematother. 1997;6:227–234
  33. Ascioglu S, Rex JH, Pauw de, et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis. 2002;34:7–14
  34. De Pauw B, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46:1813–1821
  35. Ljungman P, Griffiths P, Paya C. Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis. 2002;34:1094–1097
  36. Bozza S, Gaziano R, Bonifazi P, et al. Thymosin alpha1 activates the TLR9/MyD88/IRF7-dependent murine cytomegalovirus sensing for induction of anti-viral responses in vivo. Int Immunol. 2007;19:1261–1270
  37. Tabeta K, Georgel P, Janssen E, et al. Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc Natl Acad Sci U S A. 2004;101:3516–3521
  38. Delale T, Paquin A, Asselin-Paturel C, et al. MyD88-dependent and -independent murine cytomegalovirus sensing for IFN-alpha release and initiation of immune responses in vivo. J Immunol. 2005;175:6723–6732
  39. Novak N, Yu CF, Bussmann C, et al. Putative association of a TLR9 promoter polymorphism with atopic eczema. Allergy. 2007;62:766–772
  40. Antequera F, Tamame M, Villanueva JR, Santos T. DNA methylation in the fungi. J Biol Chem. 1984;259:8033–8036
  41. Grohmann U, Volpi C, Fallarino F, et al. Reverse signaling through GITR ligand enables dexamethasone to activate IDO in allergy. Nat Med. 2007;13:579–586
  42. Bellocchio S, Montagnoli C, Bozza S, et al. The contribution of the Toll-Like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo. J Immunol. 2004;172:3059–3069
  43. Ramirez-Ortiz ZG, Specht CA, Wang JP, et al. Toll-like receptor 9-dependent immune activation by unmethylated CpG motifs in Aspergillus fumigatus DNA. Infect Immun. 2008;76:2123–2129
  44. Sun S, Rao NL, Venable J, Thurmond R, Karlsson L. TLR7/9 antagonists as therapeutics for immune-mediated inflammatory disorders. Inflamm Allergy Drug Targets. 2007;6:223–235
  45. Kijpittayarit S, Eid AJ, Brown RA, Paya CV, Razonable RR. Relationship between Toll-like receptor 2 polymorphism and cytomegalovirus disease after liver transplantation. Clin Infect Dis. 2007;44:1315–1320
  46. Vanhinsbergh LJ, Powe DG, Jones NS. Reduction of TLR2 gene expression in allergic and nonallergic rhinitis. Ann Allergy Asthma Immunol. 2007;99:509–516
  47. Dessing MC, Schouten M, Draing C, Levi M, von Aulock S, van der Poll T. Role played by Toll-like receptors 2 and 4 in lipoteichoic acid-induced lung inflammation and coagulation. J Infect Dis. 2008;197:245–252
  48. Braedel S, Radsak M, Einsele H, et al. Aspergillus fumigatus antigens activate innate immune cells via toll-like receptors 2 and 4. Br J Haematol. 2004;125:392–399
  49. Chignard M, Balloy V, Sallenave JM, Si-Tahar M. Role of Toll-like receptors in lung innate defense against invasive aspergillosis. Distinct impact in immunocompetent and immunocompromized hosts. Clin Immunol. 2007;124:238–243
  50. Mambula SS, Sau K, Henneke P, Golenbock DT, Levitz SM. Toll-like receptor (TLR) signaling in response to Aspergillus fumigatus. J Biol Chem. 2002;277:39320–39326
  51. Netea MG, Warris A, Van der Meer JW, et al. Aspergillus fumigatus evades immune recognition during germination through loss of toll-like receptor-4-mediated signal transduction. J Infect Dis. 2003;188:320–326
  52. Candore G, Aquino A, Balistreri CR, et al. Inflammation, longevity, and cardiovascular diseases: role of polymorphisms of TLR4. Ann N Y Acad Sci. 2006;1067:282–287
  53. Romani L, Puccetti P. Controlling pathogenic inflammation to fungi. Expert Rev Anti Infect Ther. 2007;5:1007–1017
  54. Romani L, Fallarino F, De Luca A, et al. Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease. Nature. 2008;451:211–215
  55. Romani L, Zelante T, De Luca A, Fallarino F, Puccetti P. IL-17 and therapeutic kynurenines in pathogenic inflammation to fungi. J Immunol. 2008;180:5157–5162
  56. De Luca A, Montagnoli C, Zelante T, et al. Functional yet balanced reactivity to Candida albicans requires TRIF, MyD88, and IDO-dependent inhibition of Rorc. J Immunol. 2007;179:5999–6008
  57. Romani L, Puccetti P. Protective tolerance to fungi: the role of IL-10 and tryptophan catabolism. Trends Microbiol. 2006;14:183–189
  58. Trinchieri G, Sher A. Cooperation of Toll-like receptor signals in innate immune defence. Nat Rev Immunol. 2007;7:179–190

PII: S0301-472X(09)00214-8

doi: 10.1016/j.exphem.2009.06.004

Experimental Hematology
Volume 37, Issue 9 , Pages 1022-1029 , September 2009