Skip to main content
SpringerLink
Log in

Melanin in a Meristematic Mutant of Fonsecaea monophora Inhibits the Production of Nitric Oxide and Th1 Cytokines of Murine Macrophages

  • Published:
Mycopathologia Aims and scope Submit manuscript

Abstract

Melanin is a complex polymer which is secreted outside or constitutes the structure of fungal cell wall. It is considered as an important virulence factor in opportunistic pathogenic fungi. In this study, one albino mutant (CBS 125149) was generated from a parent meristematic mutant (CBS 122845) of Fonsecaea monophora. Transmission electron microscopy profiles showed that melanin in the parent strains appeared as electron-dense granules which located on the cell wall surface. We extracted the cell wall fractions from the two different strains by an alkali–acid method. The different strains or its cell wall fractions were interacted with the activated RAW264.7. The pigmented strain and its cell wall fraction could reduce the expression of inducible nitric oxide synthase gene and inhibit the synthesis of nitric oxide in vitro (P < 0.05). Exacerbated Th2 and inhibited Th1 response occurred in the interaction between activated RAW264.7 and the pigmented strain or its cell wall fraction. Collectively, our results suggest that melanin plays an important role in escaping the killing of oxidative burst in vitro. The exacerbated Th2 response probably accelerates the persistence of the fungus.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Minotto R, Bernardi CD, Mallmann LF, Edelweiss MI, Scroferneker ML. Chromoblastomycosis: a review of 100 cases in the state of Rio Grande do Sul, Brazil. J Am Acad Dermatol. 2001;44:585–92.

    Article  PubMed  CAS  Google Scholar 

  2. Xi L, Sun J, Lu C, Liu H, Xie Z, Fukushima K, et al. Molecular diversity of Fonsecaea (Chaetothyriales) causing chromoblastomycosis in southern China. Med Mycol. 2009;47:27–33.

    Article  PubMed  CAS  Google Scholar 

  3. Ameen M. Chromoblastomycosis: clinical presentation and management. Clin Exp Dermatol. 2009;34:849–54.

    Article  PubMed  CAS  Google Scholar 

  4. Morris-Jones R, Gomez BL, Diez S, Uran M, Morris-Jones SD, Casadevall A, et al. Synthesis of melanin pigment by Candida albicans in vitro and during infection. Infect Immun. 2005;73:6147–50.

    Article  PubMed  CAS  Google Scholar 

  5. Chaskes S, Tyndall RL. Pigment production by Cryptococcus neoformans and other Cryptococcus species from aminophenols and diaminobenzenes. J Clin Microbiol. 1978;7:146–52.

    PubMed  CAS  Google Scholar 

  6. Gomez BL, Nosanchuk JD, Diez S, Youngchim S, Aisen P, Cano LE, et al. Detection of melanin-like pigments in the dimorphic fungal pathogen Paracoccidioides brasiliensis in vitro and during infection. Infect Immun. 2001;69:5760–7.

    Article  PubMed  CAS  Google Scholar 

  7. Romero-Martinez R, Wheeler M, Guerrero-Plata A, Rico G, Torres-Guerrero H. Biosynthesis and functions of melanin in Sporothrix schenckii. Infect Immun. 2000;68:3696–703.

    Article  PubMed  CAS  Google Scholar 

  8. Nosanchuk JD, Gomez BL, Youngchim S, Diez S, Aisen P, Zancope-Oliveira RM, et al. Histoplasma capsulatum synthesizes melanin-like pigments in vitro and during mammalian infection. Infect Immun. 2002;70:5124–31.

    Article  PubMed  CAS  Google Scholar 

  9. Nosanchuk JD, van Duin D, Mandal P, Aisen P, Legendre AM, Casadevall A. Blastomyces dermatitidis produces melanin in vitro and during infection. FEMS Microbiol Lett. 2004;239:187–93.

    Article  PubMed  CAS  Google Scholar 

  10. Tsai HF, Fujii I, Watanabe A, Wheeler MH, Chang YC, Yasuoka Y, et al. Pentaketide melanin biosynthesis in Aspergillus fumigatus requires chain-length shortening of a heptaketide precursor. J Biol Chem. 2001;276:29292–8.

    Article  PubMed  CAS  Google Scholar 

  11. Alviano DS, Franzen AJ, Travassos LR, Holandino C, Rozental S, Ejzemberg R, et al. Melanin from Fonsecaea pedrosoi induces production of human antifungal antibodies and enhances the antimicrobial efficacy of phagocytes. Infect Immun. 2004;72:229–37.

    Article  PubMed  CAS  Google Scholar 

  12. Nosanchuk JD, Rosas AL, Casadevall A. The antibody response to fungal melanin in mice. J Immunol. 1998;160:6026–31.

    PubMed  CAS  Google Scholar 

  13. Jacobson ES. Pathogenic roles for fungal melanins. Clin Microbiol Rev. 2000;13:708–17.

    Article  PubMed  CAS  Google Scholar 

  14. Sotto MN, De Brito T, Silva AM, Vidal M, Castro LG. Antigen distribution and antigen-presenting cells in skin biopsies of human chromoblastomycosis. J Cutan Pathol. 2004;31:14–8.

    Article  PubMed  Google Scholar 

  15. Rossi GR, Cervi LA, Garcia MM, Chiapello LS, Sastre DA, Masih DT. Involvement of nitric oxide in protecting mechanism during experimental cryptococcosis. Clin Immunol. 1999;90:256–65.

    Article  PubMed  CAS  Google Scholar 

  16. Fernandes KS, Coelho AL, Lopes Bezerra LM, Barja-Fidalgo C. Virulence of Sporothrix schenckii conidia and yeast cells, and their susceptibility to nitric oxide. Immunology. 2000;101:563–9.

    Article  PubMed  CAS  Google Scholar 

  17. Lane TE, Otero GC, Wu-Hsieh BA, Howard DH. Expression of inducible nitric oxide synthase by stimulated macrophages correlates with their antihistoplasma activity. Infect Immun. 1994;62:1478–9.

    PubMed  CAS  Google Scholar 

  18. Cunha MM, Franzen AJ, Seabra SH, Herbst MH, Vugman NV, Borba LP, et al. Melanin in Fonsecaea pedrosoi: a trap for oxidative radicals. BMC Microbiol. 2010;10:80.

    Article  PubMed  Google Scholar 

  19. Mazo Fávero Gimenes V, Da Glória de Souza M, Ferreira KS, Marques SG, Gonçalves AG, Vagner de Castro Lima Santos D, et al. Cytokines and lymphocyte proliferation in patients with different clinical forms of chromoblastomycosis. Microbes Infect. 2005;7:708–13.

    Article  PubMed  Google Scholar 

  20. d’Avila SC, Pagliari C, Duarte MI. The cell-mediated immune reaction in the cutaneous lesion of chromoblastomycosis and their correlation with different clinical forms of the disease. Mycopathologia. 2003;156:51–60.

    PubMed  Google Scholar 

  21. Xi L, Lu C, Sun J, Li X, Liu H, Zhang J, et al. Chromoblastomycosis caused by a meristematic mutant of Fonsecaea monophora. Med Mycol. 2009;47:77–80.

    Article  PubMed  Google Scholar 

  22. Najafzadeh MJ, Sun J, Vicente V, Xi L, van den Ende AH, de Hoog GS. Fonsecaea nubica sp. nov, a new agent of human chromoblastomycosis revealed using molecular data. Med Mycol. 2010;48:800–6.

    Article  PubMed  CAS  Google Scholar 

  23. Alviano CS, Farbiarz ZR, De Souza W, Angluster J, Travassos LR. Characterization of Fonsecaea pedrosoi melanin. J Gen Microbiol. 1991;137:837–44.

    Article  PubMed  CAS  Google Scholar 

  24. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem. 1982;126:131–8.

    Article  PubMed  CAS  Google Scholar 

  25. Esterre P, Andriantsimahavandy A. History of a cutaneous lesion: chromomycosis. Arch Inst Pasteur Madagascar. 1993;60:21–5.

    PubMed  CAS  Google Scholar 

  26. Souza ET, Silva-Filho FC, De Souza W, et al. Identification of sialic acids on the cell surface of hyphae and conidia of the human pathogen Fonsecaea pedrosoi. J Med Vet Mycol. 1986;24:145–54.

    Article  PubMed  CAS  Google Scholar 

  27. Nóbrega YK, Lozano VF, de Araújo TS, de Carvalho DD, Bocca AL. The cell wall fraction from Fonsecaea pedrosoi stimulates production of different profiles of cytokines and nitric oxide by murine peritoneal cells in vitro. Mycopathologia. 2010;170:89–98.

    Article  PubMed  Google Scholar 

  28. Ruiz-Díez B, Martínez-Suárez JV. Isolation, characterization, and antifungal susceptibility of melanin-deficient mutants of Scedosporium prolificans. Curr Microbiol. 2003;46:228–32.

    Article  PubMed  Google Scholar 

  29. Casadevall A, Rosas AL, Nosanchuk JD. Melanin and virulence in Cryptococcus neoformans. Curr Opin Microbiol. 2000;3:354–8.

    Article  PubMed  CAS  Google Scholar 

  30. Sun J, Zhang J, Najafzadeh MJ, Badali H, Li X, Xi L, de Hoog GS. Melanization of a meristematic mutant of Fonsecaea monophora increases tolerance to stress factors while no effects on antifungal susceptibility. Mycopathologia. 2011;172:373–80.

    Article  PubMed  CAS  Google Scholar 

  31. Langfelder K, Streibel M, Jahn B, Haase G, Brakhage AA. Biosynthesis of fungal melanins and their importance for human pathogenic fungi. Fungal Genet Biol. 2003;38:143–58.

    Article  PubMed  CAS  Google Scholar 

  32. Revankar SG, Sutton DA. Melanized fungi in human disease. Clin Microbiol Rev. 2010;23:884–928.

    Article  PubMed  Google Scholar 

  33. Rozental S, Alviano CS, de Souza W. The in vitro susceptibility of Fonsecaea pedrosoi to activated macrophages. Mycopathologia. 1994;126:85–91.

    Article  PubMed  CAS  Google Scholar 

  34. Bocca AL, Brito PP, Figueiredo F, Tosta CE. Inhibition of nitric oxide production by macrophages in chromoblastomycosis: a role for Fonsecaea pedrosoi melanin. Mycopathologia. 2006;161:195–203.

    Article  PubMed  CAS  Google Scholar 

  35. Allendoerfer R, Deepe GS Jr. Intrapulmonary response to Histoplasma capsulatum in gamma interferon knockout mice. Infect Immun. 1997;65:2564–9.

    PubMed  CAS  Google Scholar 

  36. Wozniak KL, Ravi S, Macias S, Olszewski MA, Steele C, Wormley FL. Insights into the mechanisms of protective immunity against Cryptococcus neoformans infection using a mouse model of pulmonary cruptococcosis. PLoS ONE. 2009;4:e6854.

    Article  PubMed  Google Scholar 

  37. Naundorf S, Schröder M, Höflich C, Suman N, Volk HD, Grütz G. IL-10 interferes directly with TCR-induced IFN-gamma but not IL-17 production in memory T cells. Eur J Immunol. 2009;39:1435–46.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank Prof. Liangchun Wang from our Department for English polishing. This study was supported by Guangdong Provincial Science and Technology Department of scientific and technological fund (2011B080701009).

Author information

Authors and Affiliations

  1. Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 West Yanjiang Rd, Guangzhou, 510120, China

    Junmin Zhang, Li Wang, Liyan Xi, Yongxuan Hu, Xiqing Li, Xiao Huang & Sha Lu

  2. Department of Dermatology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China

    Huaiqiu Huang

  3. Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, 176 XingangXi Rd, Guangzhou, 510300, Guangdong, People’s Republic of China

    Jiufeng Sun

Authors
  1. Junmin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Li Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liyan Xi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Huaiqiu Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yongxuan Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiqing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiao Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sha Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jiufeng Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jiufeng Sun.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, J., Wang, L., Xi, L. et al. Melanin in a Meristematic Mutant of Fonsecaea monophora Inhibits the Production of Nitric Oxide and Th1 Cytokines of Murine Macrophages. Mycopathologia 175, 515–522 (2013). https://doi.org/10.1007/s11046-012-9588-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11046-012-9588-x

Keywords

Search

Navigation