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Inhibition of Nitric Oxide Production by Macrophages in Chromoblastomycosis: A Role for Fonsecaea pedrosoi Melanin

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Abstract

Chromoblastomycosis is a chronic and progressive deep mycosis that is usually found in tropical and subtropical areas. Fonsecaea pedrosoi is considered its most frequent etiologic agent and causes a typical granulomatous inflammatory response, whose degree reflects the immune status of the host. Since macrophages play a fundamental role in the control of the infection, this study aimed at investigating the production of oxygen reactive specimens, the phagocytic capacity and the production of nitric oxide (NO) by macrophages employing in vitro assays and an in vivo model of chromoblastomycosis. Our results demonstrated that, during the infection, peritoneal macrophages show an increased phagocytic capacity and H2O2 production, but also a reduced ability to produce NO. Moreover, F. pedrosoi stimulated H2O2 production in vitro but not the synthesis of NO. The incubation of IFNγ and LPS-stimulated macrophages with melanin, obtained from the fungus, inhibited NO production. Examination of the liver and spleen of infected animals, at day 30 or 60 following inoculation, showed a progressive increase in the number and size of granulomas, indicating that macrophages are properly mobilized and activated. Our data suggest that the inability of the host to clear F. pedrosoi, leading to a chronic disease, is due, at least in part, to the inhibition of NO synthesis by macrophages by fungus-produced melanin.

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References

  1. AT Londero CD Ramos (1989) ArticleTitleChromoblastomicose no interior do Rio Grande do Sul An Bras. Dermatol. 64 155–1558

    Google Scholar 

  2. P Jayalakshmi LM Loi TS SooHoo (1990) ArticleTitleChromoblastomycosis in Malasya Mycopathologia 109 27–31 Occurrence Handle10.1007/BF00437003 Occurrence Handle1:STN:280:By%2BB38%2Fot1I%3D Occurrence Handle2325747

    Article  CAS  PubMed  Google Scholar 

  3. JF Uribe AI Zuluaga W Leon A Restrepo (1989) ArticleTitleHistopathology of chromoblastomycosis Mycopathologia 105 1–7 Occurrence Handle1:STN:280:BiaB1MrltF0%3D Occurrence Handle2739689

    CAS  PubMed  Google Scholar 

  4. BC Hirsh WC Johnson (1984) ArticleTitlePathology of granulomatous diseases. Mixed inflammatory granulomas Int. J. Dermatol. 23 587–597

    Google Scholar 

  5. P Esterre S Peurol D Sainte-Maued R Padrimaud JA Grimaud (1993) ArticleTitleGranulomatous reaction and tissue remodeling in the cutaneous lesion of chromomycosis Virchows Archiv. A. Pathol. Anat. Histopathol. 422 285–291 Occurrence Handle1:STN:280:ByyB1c3htVQ%3D

    CAS  Google Scholar 

  6. AL Bittencourt AT Londero JAF Andrade (1994) ArticleTitleChromoblastomicose auricular – relato de caso Rev. Inst. Med. Trop. S. Paulo 36 381–383 Occurrence Handle1:STN:280:ByqB2cbosF0%3D Occurrence Handle7732272

    CAS  PubMed  Google Scholar 

  7. SR Farbiarz TU Carvalho C Alviano W Souza (1990) ArticleTitleFine structure and cytochemistry of interaction between Fonsecaea pedrosoi and mouse resident macrophages J. Med. Vet. Mycol. 28 373–383 Occurrence Handle1:STN:280:By6C3s3ktVM%3D Occurrence Handle2283584

    CAS  PubMed  Google Scholar 

  8. P Esterre M Jahevitra A Andriantasimahavandy (2000) ArticleTitleHumoral immune response in chromoblastomycosis during and after therapy Clin. Diagn Lab. Immunol. 7 497–500 Occurrence Handle10.1128/CDLI.7.3.497-500.2000 Occurrence Handle1:CAS:528:DC%2BD3cXjslWisL8%3D Occurrence Handle10799467

    Article  CAS  PubMed  Google Scholar 

  9. SR Farbiarz TU Carvalho C Alviano W Souza (1992) ArticleTitleInhibitory effect of melanin of the interaction of Fonsecaea pedrosoi with mammalian cell in vitro J. Med. Vet. Mycol. 30 265–273 Occurrence Handle1:STN:280:ByyD2Mfitl0%3D Occurrence Handle1432486

    CAS  PubMed  Google Scholar 

  10. DS Alviano AJ Franzen LR Travassos C Holandino S Rozental R Ejzemberg CS Alviano ML Rodrigues (2004) ArticleTitleMelanin from Fonsecaea pedrosoi induces production of human antifungal antibodies and enhances the antimicrobial efficacy of phagocytes Infect. Immun 72 229–237 Occurrence Handle10.1128/IAI.72.1.229-237.2004 Occurrence Handle1:CAS:528:DC%2BD2cXpvFem Occurrence Handle14688100

    Article  CAS  PubMed  Google Scholar 

  11. J Ahrens JR Graybill A Abishawl FO Tio MG Rinaldi (1989) ArticleTitleExperimental murine chromomycosis mimicking chronic progressive human disease Am. J. Trop. Med. Hyg. 40 651–658 Occurrence Handle1:STN:280:BiaA3c%2FpsFA%3D Occurrence Handle2742041

    CAS  PubMed  Google Scholar 

  12. S Rozental CS Alviano W Souza (1996) ArticleTitleFine structure and cytochemistry of the interaction between Fonsecaea pedrosoi and mouse resident macrophages J. Med. Vet. Mycol. 28 373–383

    Google Scholar 

  13. S Rozental CS Alviano W Souza (1994) ArticleTitleThe in vitro susceptibility of Fonsecaea pedrosoi to activated macrophages Mycopathologia 126 85–91 Occurrence Handle10.1007/BF01146200 Occurrence Handle1:STN:280:ByuA2cvit1Y%3D Occurrence Handle8065435

    Article  CAS  PubMed  Google Scholar 

  14. Y Wang P Aisen A Casadevall (1995) ArticleTitleCyptococcus neoformans melanin and virulence: mechanism of action Infect. Immun. 63 3131–3136 Occurrence Handle1:CAS:528:DyaK2MXntFyqtbo%3D Occurrence Handle7622240

    CAS  PubMed  Google Scholar 

  15. MB Silva AF Marques JD Nosanchuk A Casadervall LR Travassos CP Taborda (2006) ArticleTitleMelanin in the dimorphic fungal pathogen Paracoccidioides brasiliensis intracellular resistance and drug susceptibility Microbes Infect 8 197–205 Occurrence Handle10.1016/j.micinf.2005.07.004 Occurrence Handle16213179

    Article  PubMed  Google Scholar 

  16. CS Alviano SR Farbiarz W Souza J Angluster LR Travassos (1991) ArticleTitleCharacterization of Fonsecaea pedrosoi melanin J. Gen. Microbiol. 137 837–844 Occurrence Handle1:CAS:528:DyaK3MXisVequ7Y%3D Occurrence Handle1856679

    CAS  PubMed  Google Scholar 

  17. F Figueiredo TJ Koerner DO Adams (1989) ArticleTitleMolecular mechanisms regulating the histocompatibility molecules on macrophages J. Immunol. 143 3781–3786 Occurrence Handle1:CAS:528:DyaK3cXps1Ghtg%3D%3D Occurrence Handle2511248

    CAS  PubMed  Google Scholar 

  18. DA Horwitz AC Allison P Ward N Knight (1977) ArticleTitleIdentification of human mononuclear leucocyte populations by esterase staining Clin. Exp. Immunol. 30 289–298 Occurrence Handle1:STN:280:CSeC3croslI%3D Occurrence Handle304784

    CAS  PubMed  Google Scholar 

  19. DR Shaw PM. Griffin SuffixJr (1981) Antibody dependent and antibody independent phagocytosis DO Adams PJ Edelson H Koren (Eds) Methods for studying mononuclear phagocytes Academic Press London 511–527

    Google Scholar 

  20. E Pick D Mizel (1981) ArticleTitleRapid microassay for the measurement of superoxide and hydrogen peroxide production by macrophage in culture using an automatic enzyme immunoassay reader J. Immunol. Meth. 46 211–226 Occurrence Handle10.1016/0022-1759(81)90138-1 Occurrence Handle1:CAS:528:DyaL38Xjt12ktA%3D%3D

    Article  CAS  Google Scholar 

  21. LC Green KR Luziariaga DA Wagner N Rand N Istfan VR Yong T Tannenbaum (1981) ArticleTitleNitrate biosynthesis in man Proc. Natl. Acad. Sci. USA 78 7764–7768 Occurrence Handle1:CAS:528:DyaL38Xkslahtg%3D%3D Occurrence Handle6950416

    CAS  PubMed  Google Scholar 

  22. N Cardona-Castro P Agudelo-Florez (1999) ArticleTitleDevelopment of a chronic chromoblastomycosis model in immunocompetent mice Med. Mycol. 37 81–83 Occurrence Handle10.1046/j.1365-280X.1999.00189.x Occurrence Handle1:STN:280:DyaK1M3ptFSktA%3D%3D Occurrence Handle10361262

    Article  CAS  PubMed  Google Scholar 

  23. N Kurita (1979) ArticleTitleCell-mediated immune response in mice infected with Fonsecaea pedrosoi Mycopathologia 68 9–12 Occurrence Handle10.1007/BF00490385 Occurrence Handle1:STN:280:Bi%2BD3s3osVQ%3D Occurrence Handle386129

    Article  CAS  PubMed  Google Scholar 

  24. SCGP D’avila C Pagliari MIS Duarte (2002) ArticleTitleThe cell-mediated immune reaction in the cutaneous lesion of chromoblastomycosis and their correlation with different clinical forms of the disease Mycopathologia 156 51–60

    Google Scholar 

  25. VMF Gimenes MG Souza KS Ferreira SG Marques AG Gonçalves DVCL Santos CM Pedroso e Silva SR Almeida (2005) ArticleTitleCytokines and lymphocyte proliferation in patients with the different clinical forms of chromoblastomycosis Microb. Infect. 7 708–713 Occurrence Handle1:CAS:528:DC%2BD2MXkt1Gnsbg%3D

    CAS  Google Scholar 

  26. JW Murphy (2001) ArticleTitleMechanisms of natural resistance of human pathogenic fungi Annu. Rev. Microbiol. 45 509–538

    Google Scholar 

  27. MN Sotto T Brito AMG Silva M Vidal LG Martins Castro (2004) ArticleTitleAntigen distribution and antigen-presenting cell in skin biopsies of human chromoblastomycosis J. Cutan. Pathol. 31 14–18 Occurrence Handle10.1046/j.0303-6987.2004.0131.x Occurrence Handle14675280

    Article  PubMed  Google Scholar 

  28. J Rivera J Mukherjee LM Weiss A Casadevall (2002) ArticleTitleAntibody efficacy in murine pulmonary Cryptococcus neoformans infection: a role for nitric oxide J. Immunol. 168 3419–3427 Occurrence Handle1:CAS:528:DC%2BD38Xis1ajt7w%3D Occurrence Handle11907100

    CAS  PubMed  Google Scholar 

  29. A Vázquez-Torres E Balish (1997) ArticleTitleMacrophages in resistance to candidiasis Microbiol. Mol. Biol. Rev. 61 170–192 Occurrence Handle9184009

    PubMed  Google Scholar 

  30. AL Bocca EE Hayashi AG Pinheiro AB Furlanetto AP Campanelli FQ Cunha F Figueiredo (1998) ArticleTitleTreatment of Paracoccidioides brasiliensis-infected mice with the nitric oxide inhibitor prevents the failure of cell-mediated immune response J. Immunol. 161 3056–3063 Occurrence Handle1:CAS:528:DyaK1cXmtVGmsrg%3D Occurrence Handle9743371

    CAS  PubMed  Google Scholar 

  31. B Philippe O Ibrahim-Granet MC Prevost MA Gougerot-Pocidalo M Sanchez Perez A Meeren ParticleVan de JP Latge (2003) ArticleTitleKilling of Aspergillus fumigatus by alveolar macrophages is mediated by reactive oxidant intermediates Infect Immun. 71 3034–3042 Occurrence Handle10.1128/IAI.71.6.3034-3042.2003 Occurrence Handle1:CAS:528:DC%2BD3sXkt1Kqt7w%3D Occurrence Handle12761080

    Article  CAS  PubMed  Google Scholar 

  32. E Brummer DA Stevens (1995) ArticleTitleAntifungal mechanisms of activated murine bronchoalveolar or peritoneal macrophages for Histoplasma capsulatum Clin. Exp. Immunol. 102 65–70 Occurrence Handle1:STN:280:BymD3czpsFY%3D Occurrence Handle7554402

    CAS  PubMed  Google Scholar 

  33. SJ Green CA Nacy (1993) ArticleTitleAntimicrobial and immunopathologic effects of cytokine-induced nitric oxide synthesis Curr. Opin. Infect. Dis. 6 384–394

    Google Scholar 

  34. FQ Cunha S Moncada FY Liew (1992) ArticleTitleInterleukin-10 (IL-10) inhibits the induction of nitric oxide synthase by interferon-γ in murine macrophages Biochem. Biophys. Res. Commun. 182 1155–1159 Occurrence Handle10.1016/0006-291X(92)91852-H Occurrence Handle1:CAS:528:DyaK38Xht1Klsb4%3D Occurrence Handle1371674

    Article  CAS  PubMed  Google Scholar 

  35. FY Liew Y Li A Severn S Millott J Schmidt M Salter S Moncada (1991) ArticleTitleA possible novel pathway of regulation by murine T helper type-2 (Th2) cells of a Th1 cell activity via the modulation of the induction of nitric oxide synthase on macrophages Eur. J. Immunol. 21 2489–2494 Occurrence Handle1:CAS:528:DyaK3MXmslOqs7o%3D Occurrence Handle1717284

    CAS  PubMed  Google Scholar 

  36. MG Netea R Sutmuller C Hermann CAA Graaf ParticleVan der JWM Meer ParticleVan der JH Krieken ParticleVan T Hartung G Adema BJ Kullberg (2004) ArticleTitleToll-like receptor 2 suppresses immunity against Candida albicans through induction of IL-10 and regulatory T cells J. Immunol. 172 3712–3718 Occurrence Handle1:CAS:528:DC%2BD2cXhvVKis7k%3D Occurrence Handle15004175

    CAS  PubMed  Google Scholar 

  37. E Blasi A Mucci R Neglia F Pezzini B Colombari D Radzioch A Cossarizza E Lugli G Volpini GD Giudice S Peppoloni (2005) ArticleTitleBiological importance of the toll-like receptors, TLR2 and TLR4, in macrophage response to infection with Candida albicans FEMS Immunol. Med. Mycol. 44 69–79 Occurrence Handle1:CAS:528:DC%2BD2MXisVWqu7s%3D

    CAS  Google Scholar 

  38. S Shoham C Huang JM Chen DT golenbock SM Levitz (2001) ArticleTitleToll-like receptor 4 mediates intracellular signaling without TNF release in response to Cryptococcus neoformans polyssacharide capsule J. Immunol. 166 4620–4626 Occurrence Handle1:CAS:528:DC%2BD3MXit1OktLk%3D Occurrence Handle11254720

    CAS  PubMed  Google Scholar 

  39. A Meier CJ Kirschning T Nikolaus H Wagner J Heesemann F Ebel (2003) ArticleTitleToll-like receptor (TLR)2 and TLR4 are essencial for aspergillus-induced activation of murine macrophage Cell Microbiol. 5 561–570 Occurrence Handle10.1046/j.1462-5822.2003.00301.x Occurrence Handle1:CAS:528:DC%2BD3sXmtVyktLw%3D Occurrence Handle12864815

    Article  CAS  PubMed  Google Scholar 

  40. CL Silva SM Ekizlerian (1985) ArticleTitleGranulomatous reaction induced by lipids extracted from Fonsecaea pedrosoi, Fonsecaea conipactum, Clasdosporium carrionii and Phialophora verrucosa J. Gen. Microbiol. 131 187–194 Occurrence Handle1:CAS:528:DyaL2MXitFOqtLk%3D Occurrence Handle3989508

    CAS  PubMed  Google Scholar 

  41. CL Silva RA Fazioli (1985) ArticleTitleRole of the fungal cell wall in the granulomatous response of mice to the agents of chromomycosis J. Med. Microbiol. 20 299–305 Occurrence Handle1:STN:280:BimD283lvVI%3D Occurrence Handle4068024

    CAS  PubMed  Google Scholar 

  42. N Mohagheghpour N Wlesh SJ Garger L Dousman LK Grill D Tusé (2000) ArticleTitleSynthetic melanin suppresses production of proinflammatory cytokines Cell Immunol. 199 25 Occurrence Handle10.1006/cimm.1999.1599 Occurrence Handle1:CAS:528:DC%2BD3cXhtFWjsrg%3D Occurrence Handle10675272

    Article  CAS  PubMed  Google Scholar 

  43. EJ Jacobson (2000) ArticleTitlePathogenic roles for fungal melanins Clin. Microbiol. Rev. 13 708–717 Occurrence Handle10.1128/CMR.13.4.708-717.2000 Occurrence Handle1:CAS:528:DC%2BD3cXnslCgtbk%3D Occurrence Handle11023965

    Article  CAS  PubMed  Google Scholar 

  44. E Reiss W Nickersson (1974) ArticleTitleControl of dimorphism in Phialophora verrucosa Sabouraudia 12 202–213 Occurrence Handle1:STN:280:CSuB1Mbnt1c%3D Occurrence Handle4851175

    CAS  PubMed  Google Scholar 

  45. Y Wang A Casadevall (1994) ArticleTitleSusceptibility of melanized and nonmelanized Cryptococcus neoformans to nitrogen- and oxygen-derived oxidants Infect. Immun. 62 3004–3007 Occurrence Handle1:CAS:528:DyaK2cXlvFOrsLo%3D Occurrence Handle8005689

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Cell Biology, Institute of Biology, University of Brasília, Brasilia, CEP 70910-900, DF, Brazil

    Anamelia L. Bocca

  2. Area of Pathology, Faculty of Medicine, University of Brasilia, Brasilia, Brazil

    Patrícia P. M. S. Brito, Florêncio Figueiredo & Carlos Eduardo Tosta

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  1. Anamelia L. Bocca
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  2. Patrícia P. M. S. Brito
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  3. Florêncio Figueiredo
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Correspondence to Anamelia L. Bocca.

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Bocca, A.L., Brito, P.P.M.S., Figueiredo, F. et al. Inhibition of Nitric Oxide Production by Macrophages in Chromoblastomycosis: A Role for Fonsecaea pedrosoi Melanin. Mycopathologia 161, 195–203 (2006). https://doi.org/10.1007/s11046-005-0228-6

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