Aspergillus fumigatus conidial melanin modulates host cytokine response.

Louis Y A Chai, Mihai G Netea, Janyce Sugui, Alieke G Vonk, Wendy W J van de Sande, Adilia Warris, Kyung J Kwon-Chung, Bart Jan Kullberg
Author Information
  1. Louis Y A Chai: Department of Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101, Geert Grootplein 8, 6525 GA, Nijmegen, The Netherlands.

Abstract

Melanin biopigments have been linked to fungal virulence. Aspergillus fumigatus conidia are melanised and are weakly immunogenic. We show that melanin pigments on the surface of resting Aspergillus fumigatus conidia may serve to mask pathogen-associated molecular patterns (PAMPs)-induced cytokine response. The albino conidia induced significantly more proinflammatory cytokines in human peripheral blood mononuclear cells (PBMC), as compared to melanised wild-type conidia. Blocking dectin-1 receptor, Toll-like receptor 4 or mannose receptor decreased cytokine production induced by the albino but not by the wild type conidia. Moreover, albino conidia stimulated less potently, cytokine production in PBMC isolated from an individual with defective dectin-1, compared to the stimulation of cells isolated from healthy donors. These results suggest that β-glucans, but also other stimulatory PAMPs like mannan derivatives, are exposed on conidial surface in the absence of melanin. Melanin may play a modulatory role by impeding the capability of host immune cells to respond to specific ligands on A. fumigatus.

References

  1. Mol Microbiol. 1997 Oct;26(1):175-83 [PMID: 9383199]
  2. Microbes Infect. 2007 Jul;9(9):1114-23 [PMID: 17644456]
  3. Curr Opin Microbiol. 2000 Aug;3(4):354-8 [PMID: 10972493]
  4. J Med Vet Mycol. 1987 Apr;25(2):97-106 [PMID: 3598824]
  5. J Infect Dis. 2007 Nov 15;196(10):1565-71 [PMID: 18008237]
  6. J Infect Dis. 2003 Jul 15;188(2):320-6 [PMID: 12854089]
  7. Infect Immun. 1997 Dec;65(12):5110-7 [PMID: 9393803]
  8. Nat Rev Immunol. 2004 Jan;4(1):1-23 [PMID: 14661066]
  9. Rev Iberoam Micol. 2005 Mar;22(1):1-23 [PMID: 15813678]
  10. J Bacteriol. 1969 Jun;98(3):996-1004 [PMID: 4182532]
  11. PLoS Pathog. 2005 Nov;1(3):e30 [PMID: 16304610]
  12. Med Microbiol Immunol. 1998 Oct;187(2):79-89 [PMID: 9832321]
  13. Trends Microbiol. 2001 Aug;9(8):382-9 [PMID: 11514221]
  14. Antimicrob Agents Chemother. 2007 Mar;51(3):1048-54 [PMID: 17178797]
  15. Fungal Genet Biol. 2003 Mar;38(2):143-58 [PMID: 12620252]
  16. Infect Immun. 2001 Mar;69(3):1781-94 [PMID: 11179356]
  17. J Bacteriol. 1998 Jun;180(12):3031-8 [PMID: 9620950]
  18. Infect Immun. 2000 Jun;68(6):3736-9 [PMID: 10816538]
  19. J Med Microbiol. 2004 Mar;53(Pt 3):175-181 [PMID: 14970241]
  20. Infect Immun. 2007 Oct;75(10):4831-7 [PMID: 17606598]
  21. Eur J Immunol. 2003 Feb;33(2):532-8 [PMID: 12645952]
  22. Clin Infect Dis. 1998 Apr;26(4):781-803; quiz 804-5 [PMID: 9564455]
  23. Med Mycol. 2009 May;47(3):227-36 [PMID: 18654922]
  24. Cell Microbiol. 2003 Apr;5(4):203-23 [PMID: 12675679]
  25. Cell Microbiol. 2007 Feb;9(2):368-81 [PMID: 16953804]
  26. Med Mycol. 2009;47 Suppl 1:S104-9 [PMID: 18686165]
  27. J Bacteriol. 1982 Jun;150(3):1414-21 [PMID: 6804444]
  28. J Bacteriol. 1999 Oct;181(20):6469-77 [PMID: 10515939]
  29. Med Mycol. 2006 Sep 1;44(Supplement_1):S229-S235 [PMID: 30408908]
  30. Nat Rev Microbiol. 2008 Jan;6(1):67-78 [PMID: 18079743]
  31. Clin Microbiol Rev. 2000 Oct;13(4):708-17 [PMID: 11023965]
  32. J Immunol. 2006 Mar 15;176(6):3717-24 [PMID: 16517740]

Grants

  1. /Intramural NIH HHS

MeSH Term

Aspergillosis
Aspergillus fumigatus
Cells, Cultured
Cytokines
Host-Pathogen Interactions
Humans
Leukocytes, Mononuclear
Melanins
Spores, Fungal
Virulence

Chemicals

Cytokines
Melanins

Word Cloud

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