Mycopathologia

, Volume 168, Issue 1, pp 1–10 | Cite as

Current Research on the Immune Response to Experimental Sporotrichosis

  • Iracilda Zeppone Carlos
  • Micheli Fernanda Sassá
  • Diana Bridon da Graça Sgarbi
  • Marisa Campos Polesi Placeres
  • Danielle Cardoso Geraldo Maia
Article

Abstract

Sporotrichosis is often manifested as a chronic granulomatous infection and the monocytes/macrophages play a central role in the host defense system. Surface components of Sporothrix schenckii have been characterized and suggestions have been made as to their possible role in pathogenicity. Ergosterol peroxide, cell-wall compounds (alkali-insoluble fraction-F1 and lipid extract-LEY), and exoantigen from the yeast form of the fungus have been characterized as virulence factors, activating both innate, by cytotoxins linked to the activation of reactive oxygen and nitrogen species (H2O2 and NO), and adaptive immune response to produce cytokines Th1 and Th2 profile. In this study, preliminary results have demonstrated that, in systemic sporotrichosis, TLR-4 triggers the innate immune response, activating an oxidative burst. These data represent the first report of the participation of TLR-4 in murine sporotrichosis, in the presence of lipids from the cell wall of S. schenckii. These results taken together may open new perspectives of study leading to an antifungal agent that could be used to benefit the entire population.

Keywords

Sporothrix schenckii Systemic infection Cytokines Nitric oxide Hydrogen peroxide TLR-4 Th1/Th2 response 

Notes

Acknowledgments

The authors are grateful to Fundação de amparo à pesquisa do Estado de São Paulo (FAPESP) and Programa de Apoio ao Desenvolvimento científico da Faculdade (PADC)-FCF-Unesp for their financial support.

References

  1. 1.
    Schenck B. On refractory subcutaneous abscesses caused by a fungus possibly related to sporotrichia. John Hopkins Hosp. 1898;9:286–90.Google Scholar
  2. 2.
    Morris-Jones R. Sporotrichosis. Clin Dermatol. 2002;27:427–31. doi: 10.1046/j.1365-2230.2002.01087.x.CrossRefGoogle Scholar
  3. 3.
    Kauffmann CA. Sporotrichosis. Clin Infect Dis. 1999;29:231–6. doi: 10.1086/520190.CrossRefGoogle Scholar
  4. 4.
    Rivitti EA, Aoki V. Deep fungal infections in tropical countries. Clin Dermatol. 1999;17:171–90. doi: 10.1016/S0738-081X(99)00010-3.PubMedCrossRefGoogle Scholar
  5. 5.
    Belknap BS. Sporotrichosis. Dermatol Clin. 1989;7:193–202.PubMedGoogle Scholar
  6. 6.
    Carvalho MT, De Castro AP, Baby C, Werner B, Filus Neto J, Queiroz-Telles F. Disseminated cutaneous sporotrichosis in a patient with AIDS: report of a case. Rev Soc Bras Med Trop. 2002;35:655–9.PubMedGoogle Scholar
  7. 7.
    De Araújo T, Marques AC, Ferdel F. Sporotrichosis. Int J Dermatol. 2001;40:737–42. doi: 10.1046/j.1365-4362.2001.01295.x.PubMedCrossRefGoogle Scholar
  8. 8.
    Reed KD, Moore FM, Geiger GE, Stemper ME. Zoonotic transmission of sporotrichosis: a case report and review. Clin Infect Dis. 1993;16:384–7.PubMedGoogle Scholar
  9. 9.
    Dixon DM, Salkin IF, Duncan RA, Hurd NJ, Haines JH, Kemna ME, et al. Isolation and characterization of Sporothrix schenckii from clinical and environmental sources associated with the largest U.S. epidemic of sporotrichosis. J Clin Microbiol. 1991;29:1106–13.PubMedGoogle Scholar
  10. 10.
    Rippon JW. Sporotrichosis. In: Rippon JW, editor. Medical mycology: the pathogenic fungi and the pathogenic actinomyces. Chicago: W. B. Sounders; 1982. p. 277–302.Google Scholar
  11. 11.
    Da Rosa ACM, Scroferneker ML, Vettorato R, Gervini RL, Vettorato G, Weber A. Epidemiology of sporotrichosis: a study of 304 cases in Brazil. J Am Acad Dermatol. 2005;52:451–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Kauffman CA, Hajjeh R, Chapman SW. Practice guidelines for the management of patients with sporotrichosis. Clin Infect Dis. 2000;30:684–7. doi: 10.1086/313751.PubMedCrossRefGoogle Scholar
  13. 13.
    Rocha MM, Dassin T, Lira R, Lima EL, Severo LC, Londero AT. Sporotrichosis in patient with AIDS: report of a case and review. Rev Iberoam Micol. 2001;18:133–6.PubMedGoogle Scholar
  14. 14.
    Silva-Vergara ML, Maneira FR, De Oliveira RM, Santos CT, Etchebehere RM, Adad SJ. Multifocal sporotrichosis with meningeal involvement in a patient with AIDS. Med Mycol. 2005;43:187–90. doi: 10.1080/13693780500035904.PubMedCrossRefGoogle Scholar
  15. 15.
    Lopes-Bezerra LM, Schubach A, Costa RO. Sporothrix schenckii and Sporotrichosis. Ann Brazil Acad Sci. 2006;78:293–308.Google Scholar
  16. 16.
    Uenotsuchi T, Takeuchi S, Matsuda T, Urabe K, Koga T, Uchi H, et al. Differential induction of Th1-prone immunity by human dendritic cells activated with Sporothrix schenckii of cutaneous and visceral origins to determine their different virulence. Int Immunol. 2006;18:1637–46. doi: 10.1093/intimm/dxl097.PubMedCrossRefGoogle Scholar
  17. 17.
    Fernandes KSS, Mathews HL, Lopes-Bezerra LM. Differences in virulence of Sporothrix schenckii conidia related to culture conditions and cell-wall components. J Med Microbiol. 1999;49:195–203.CrossRefGoogle Scholar
  18. 18.
    Tsuboi R, Sanada T, Ogawa H. Influence of culture médium pH and proteinases inhibitors on extracellular proteinase activity and cell growth of Sporothrix schenckii. Clin Microbiol. 1988;26:1431–3.Google Scholar
  19. 19.
    Tsuboi R, Sanada T, Takamori K, Ogawa H. Isolation and properties of extracellular proteinases from Sporothrix schenckii. J Bacteriol. 1987;169:4104–9.PubMedGoogle Scholar
  20. 20.
    Yoshiike T, Lei P-C, Komatsuzaki H, Ogawa H. Antibody raised against extracellular proteinases of Sporothrix schenckii in S. schenckii inoculated hairless mice. Mycopathologia. 1993;123:69–73. doi: 10.1007/BF01365082.PubMedCrossRefGoogle Scholar
  21. 21.
    Cardoso DBS, Angluster J, Travassos LR, Alviano CS. Isolation and characterization of a glucocerebroside monoglucosylceramide from Sporothrix schenckii. FEMS Microbiol Lett. 1987;43:279–82. doi: 10.1111/j.1574-6968.1987.tb02158.x.CrossRefGoogle Scholar
  22. 22.
    Travassos LR. Sporothrix schenckii. In: Szaniszlo PJ, editor. Fungal dimorphism. New York: Plenum Publishing Corporation; 1985. p. 121–63.Google Scholar
  23. 23.
    Sgarbi DB, da Silva AJ, Carlos IZ, Silva CL, Angluster J, Alviano CS. Isolation of ergosterol peroxide and its reversion to ergosterol in the pathogenic fungus Sporothrix schenckii. Mycopathologia. 1997;139:9–14. doi: 10.1023/A:1006803832164.PubMedCrossRefGoogle Scholar
  24. 24.
    Bates ML, Reid WW, White JD. Duality of pathways in the oxidation of ergosterol to its peroxide in vivo. J Chem Soc Chem Comm. 1976;44–5.Google Scholar
  25. 25.
    Teng JI, Smith LL. Sterol metabolism. XXIV. On the unlikely participation of singlet molecular oxygen in several enzyme oxygenations. J Am Chem Soc. 1973;95:4060–1. doi: 10.1021/ja00793a045.PubMedCrossRefGoogle Scholar
  26. 26.
    Ramasarma T. H2O2 has a role in cellular regulation. Indian J Biochem Biophys. 1990;27:269–74.PubMedGoogle Scholar
  27. 27.
    Forman HJ, Torres M. Signaling by the respiratory burst in macrophages. IUBMB Life. 2001;51:365–71. doi: 10.1080/152165401753366122.PubMedCrossRefGoogle Scholar
  28. 28.
    Gillman BM, Batchelder J, Flaherty P, Weidanz WP. Suppression of Plasmodium chabaudi parasitemia is independent of the action of reactive oxygen intermediates and/or nitric oxide. Infect Immun. 2004;72:6359–66. doi: 10.1128/IAI.72.11.6359-6366.2004.PubMedCrossRefGoogle Scholar
  29. 29.
    Netea MG, Van Der Graaf CA, Vonk AG, Verschueren I, Van Der Meer JW, Kullberg BJ. The role of toll-like receptor (TLR) 2 and TLR4 in the host defense against disseminated candidiasis. J Infect Dis. 2002;185:1483–9. doi: 10.1086/340511.PubMedCrossRefGoogle Scholar
  30. 30.
    Deep GS Jr, Gibbons RS. Protective and memory immunity to Histoplasma capsulatum in absence of IL-10. J Immunol. 2003;171:5353–62.Google Scholar
  31. 31.
    Takeda K, Kaisho T, Akira S. Toll-like receptors. Annu Rev Immunol. 2003;21:335–76. doi: 10.1146/annurev.immunol.21.120601.141126.PubMedCrossRefGoogle Scholar
  32. 32.
    Medzhitov R, Preston-Hurlburt P, Janeway CA Jr. A human homologue of the Drosophila toll protein signals activation of adaptative immunity. Nature. 1997;388:394–7. doi: 10.1038/41131.PubMedCrossRefGoogle Scholar
  33. 33.
    Medzhitov R, Janeway CA Jr. The toll receptor family and microbial recognition. Trends Microbiol. 2000;8:452–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Remer KA, Brcic M, Jungi TW. Toll-like receptor-4 is involved in eliciting an LPS-induced oxidative burst in neutrophils. Immunol Lett. 2003;85:75–80. doi: 10.1016/S0165-2478(02)00210-9.PubMedCrossRefGoogle Scholar
  35. 35.
    Fantone JC, Ward PA. Role of oxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions. Am J Pathol. 1982;107:397–418.Google Scholar
  36. 36.
    Lee M, Yea SS. Hydrogen peroxide inhibits the immune response to lipopolysaccharide by attenuating signaling through c-Jun N-terminal kinase and p38 associated with protein kinase C. Immunopharmacology. 2000;48:165–72. doi: 10.1016/S0162-3109(00)00202-2.PubMedCrossRefGoogle Scholar
  37. 37.
    Carlos IZ, Sgarbi DBG, Santos GC, Placeres MCP. Sporothrix schenckii lipid inhibits macrophage phagocytosis: involvement of nitric oxide and tumor necrosis factor-α. Scand J Immunol. 2003;57:214–20. doi: 10.1046/j.1365-3083.2003.01175.x.PubMedCrossRefGoogle Scholar
  38. 38.
    Koga T, Duan H, Furue M. Immunohistochemical detection of interferon-γ-producing cells in granuloma formation of sporotrichosis. Med Mycol. 2002;40:111–4. doi: 10.1080/714031087.PubMedCrossRefGoogle Scholar
  39. 39.
    Cunningham KM, Bulmer GS, Rhoades ER. Phagocytosis and intracellular fate of Sporothrix schenckii. J Infect Dis. 1979;140:815–7.PubMedGoogle Scholar
  40. 40.
    Shiraishi A, Nakagaki K, Arai T. Role of cell-mediated immunity in the resistance to experimental sporotrichosis in mice. Mycopathologia. 1992;120:15–21. doi: 10.1007/BF00578497.PubMedCrossRefGoogle Scholar
  41. 41.
    Carlos IZ, Sgarbi DB, Angluster J, Alviano CS, Silva CL. Detection of cellular immunity with the soluble antigen of the fungus Sporothrix schenckii in the systemic form of the disease. Mycopathologia. 1992;117:139–44. doi: 10.1007/BF00442774.PubMedCrossRefGoogle Scholar
  42. 42.
    Eigler A, Greten TF, Sinha B, Haslberger C, Sullivan GW, Endres S. Endogenous adenosine curtails lipopolysaccharide-stimulated tumour necrosis factor synthesis. Scand J Immunol. 1997;45:132–9. doi: 10.1046/j.1365-3083.1997.d01-377.x.PubMedCrossRefGoogle Scholar
  43. 43.
    Carlos IZ, Zini MMC, Sgarbi DBG, Angluster J, Alviano CS, Silva CL. Disturbances in the production of interleukin-1 and tumor necrosis factor in disseminated murine sporotrichosis. Mycopathologia. 1994;127:189–94. doi: 10.1007/BF01102920.PubMedCrossRefGoogle Scholar
  44. 44.
    Palladino MA, Bahjat FR, Theodorakis EA, Moldawer LL. Anti TNF-α therapies: the next generation. Nat Rev Drug Disc. 2003;2:736–46. doi: 10.1038/nrd1175.CrossRefGoogle Scholar
  45. 45.
    Carlos IZ, Sgarbi DBG, Placeres MCP. Host organism defense by peptide-polysaccharide extracted from the fungus Sporothrix schenckii. Mycopathologia. 1999;144:9–14. doi: 10.1023/A:1006964516334.CrossRefGoogle Scholar
  46. 46.
    Parslow TG, Bainton DF, Innate immunity. In: Medical immunology. Appleton & Lange, Stanford, CT. 1997:25–42.Google Scholar
  47. 47.
    Hibbs JB, Taintor RR, Vavrin Z, Rachlin EM. Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun. 1988;157:87–94. doi: 10.1016/S0006-291X(88)80015-9.PubMedCrossRefGoogle Scholar
  48. 48.
    Johnston RB. Current concepts in immunology: monocytes and macrophages. N Engl J Med. 1988;318:747–52.PubMedGoogle Scholar
  49. 49.
    Laskin JD, Heck DE, Laskin DL. Multifunctional role of nitric oxide in inflammation. Trends Endocrinol Metab. 1994;5:377–82. doi: 10.1016/1043-2760(94)90105-8.PubMedCrossRefGoogle Scholar
  50. 50.
    Funcht DM, Fukao T, Bogdan C, Schindler H, O’Shea JJ, Koyasu S. IFN-gamma production by antigen-presenting cells: mechanisms emerge. Trends Immunol. 2001;22:556–60. doi: 10.1016/S1471-4906(01)02005-1.CrossRefGoogle Scholar
  51. 51.
    Hibbs JB Jr, Vavrin Z, Taintor RR. l-Arginine is required for expression of the activated macrophage effector mechanism causing selective metabolic inhibition in target cells. J Immunol. 1987;138:550–65.PubMedGoogle Scholar
  52. 52.
    Kudeken N, Kawakami K, Saito A. Different susceptibilities of yeasts and conidia of Penicillium marneffei to nitric oxide (NO)-mediated fungicidal activity of murine macrophages. Clin Exp Immunol. 1998;112:287–93. doi: 10.1046/j.1365-2249.1998.00565.x.PubMedCrossRefGoogle Scholar
  53. 53.
    Brummer E, Stevens DA. Antifungal mechanisms of activated murine bronchoalveolar and peritoneal macrophages for Histoplasma capsulatum. Clin Exp Immunol. 1995;102:65–70.PubMedGoogle Scholar
  54. 54.
    Wang Y, Casadevall A. Susceptibility of melanized and nonmelanized Cryptococcus neoformans to nitrogen- and oxygenderived oxidants. Infect Immun. 1994;62:3004–5.PubMedGoogle Scholar
  55. 55.
    Blasi E, Pitzurra L, Puliti M, Chimienti AR, Mazolla R, Barluzzi R, et al. Differential susceptibility of yeast and hyphal forms of Candida albicans to macrophage-derived nitrogen-containing compounds. Infect Immun. 1995;63:1806–10.PubMedGoogle Scholar
  56. 56.
    Fernandes KSS, Coelho ALJ, 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. doi: 10.1046/j.1365-2567.2000.00125.x.PubMedCrossRefGoogle Scholar
  57. 57.
    Fernandes KSS, Helal Neto E, Brito MMS, Silva JS, Cunha FQ, Barja-Fidalgo C. Detrimental role of endogenous nitric oxide in host defense against Sporothrix schenckii. Immunology. 2008;123:469–79. doi: 10.1111/j.1365-2567.2007.02712.x.PubMedCrossRefGoogle Scholar
  58. 58.
    Myers JT, Tsang AW, Swanson JA. Localized reactive oxygen and nitrogen intermediates inhibit escape of Listeria monocytogenes from vacuoles in activated macrophages. J Immunol. 2003;171:5447–53.PubMedGoogle Scholar
  59. 59.
    Kolb JP, Paul-Eugene N, Damais C, Yamaoka K, Drapier JC, Dugas B. Interleukin-4 stimulates cGMP production by IFN-gamma-activated human monocytes. Involvement of the nitric oxide synthase pathway. J Biol Chem. 1994;269:9811–6.PubMedGoogle Scholar
  60. 60.
    Bogdan C. Nitric oxide and the immune response. Nat Immunol. 2001;2:907–16. doi: 10.1038/ni1001-907.PubMedCrossRefGoogle Scholar
  61. 61.
    Kristof AS, Marks-Konczalic J, Moss J. Mitogen-activated protein kinases mediate activator protein-1-dependent human inducible nitric-oxide synthase promoter activation. J Biol Chem. 2001;276:8445–52. doi: 10.1074/jbc.M009563200.PubMedCrossRefGoogle Scholar
  62. 62.
    Okuda Y, Sakoda S, Shimaoka M, Yanagihara T. Nitric oxide induces apoptosis in mouse splenic T lymphocytes. Immunol Lett. 1996;52:135–8. doi: 10.1016/0165-2478(96)02597-7.PubMedCrossRefGoogle Scholar
  63. 63.
    Albina JE, Cui S, Mateo RB, Reichner JS. Nitric oxide-mediated apoptosis in murine peritoneal macrophages. J Immunol. 1993;150:5080–5.PubMedGoogle Scholar
  64. 64.
    Cunha FQ, Poole S, Lorenzetti BB, Ferreira SH. The pivotal role of tumour necrosis factor alpha in the development of inflammatory hyperalgesia. Br J Pharmacol. 1992;107:660–4.PubMedGoogle Scholar
  65. 65.
    Mosmann TR, Coffman RL. Th1 and Th2 cells: different patterns of lymphokine secretion lead to different functional properties. Ann Rev Immunol. 1989;7:145–74. doi: 10.1146/annurev.iy.07.040189.001045.CrossRefGoogle Scholar
  66. 66.
    Rengarajan J, Szabo SJ, Glimcher LH. Transcriptional regulation of Th1/Th2 polarization. Immunol Today. 2000;21:479–83. doi: 10.1016/S0167-5699(00)01712-6.PubMedCrossRefGoogle Scholar
  67. 67.
    Abbas AK, Lichttman AH. Cellular and molecular immunology. 6th ed. Philadelphia: W. B. Saunders; 2007. p. 572.Google Scholar
  68. 68.
    Taylor-Robinson AW, Liew FY, Severn A, Xu D, McSorley SJ, Garside P, et al. Regulation of the immune response by nitric oxide differentially produced by T helper type 1 and T helper type 2 cells. Eur J Immunol. 1994;24:980–4. doi: 10.1002/eji.1830240430.PubMedCrossRefGoogle Scholar
  69. 69.
    Brüne B, Von Knethen A, Sandau KB. Nitric oxide and its role in apoptosis. Eur J Pharmacol. 1998;26:261–72. doi: 10.1016/S0014-2999(98)00274-X.CrossRefGoogle Scholar
  70. 70.
    Cox GW, Melillo G, Chattopadhyay U, Mullet D, Fertel RH, Varesio L. Tumor necrosis factor-alpha-dependent production of reactive nitrogen intermediates mediates IFN-gamma plus IL-2-induced murine macrophage tumoricidal activity. J Immunol. 1992;15:3290–6.Google Scholar
  71. 71.
    Green K, Campbell G. Nitric oxide formation is involved in vagal inhibition of the stomach of the trout (Salmo gairdneri). J Auton Nerv Syst. 1994;15:221–9. doi: 10.1016/0165-1838(94)90012-4.CrossRefGoogle Scholar
  72. 72.
    Gazzinelli RT, Hieny S, Wynn TA, Wolf S, Sher A. Interleukin-12 is required for the T-lymphocyte-independent induction of interferon γ by an intracellular parasite and induces resistance in T-cell-deficient hosts. Proc Natl Acad Sci USA. 1993;90:6115–9. doi: 10.1073/pnas.90.13.6115.PubMedCrossRefGoogle Scholar
  73. 73.
    Trinchieri G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol. 2003;3:133–46. doi: 10.1038/nri1001.PubMedCrossRefGoogle Scholar
  74. 74.
    Mencacci A, Cenci E, Bacci A, Montagnoli C, Bistoni F, Romani L. Cytokines in candidiasis and aspergillosis. Curr Pharm Biotechnol. 2000;1:235–51. doi: 10.2174/1389201003378924.PubMedCrossRefGoogle Scholar
  75. 75.
    Hamilton TA, Becton DL, Somers SD, Gray PW, Adams DO. Interferon-gamma modulates protein kinase C activity in murine peritoneal macrophages. J Biol Chem. 1985;260:1378–81.PubMedGoogle Scholar
  76. 76.
    Cenci E, Mencacci A, Del Sero G, Bacci A, Montagnoli C, D’ostiani CF, et al. The human immune response during cutaneous leishmaniasis: NO problem. Parasitol Today. 1998;6:1957–68.Google Scholar
  77. 77.
    Puddu P, Fantuzzi L, Borghi P, Varão B, Rainaldi G, Guillemard E, et al. IL-12 induces IFN-γ expression and secretion in mouse peritoneal macrophages. J Immunol. 1997;159:3490–7.PubMedGoogle Scholar
  78. 78.
    Munder M, Mallo M, Eichmann K, Modolell M. Murine macrophages secrete interferon γ upon combined stimulation with interleukin (IL)-12 and IL-18: a novel pathway of autocrine macrophage activation. J Exp Med. 1998;187:2103–8. doi: 10.1084/jem.187.12.2103.PubMedCrossRefGoogle Scholar
  79. 79.
    Ohteki T, Fukao T, Suzue K, Maki C, Ito M, Nakamura M, et al. Interleukin-12-dependent interferon γ production by CD8α+ lymphoid dendritic cells. J Exp Med. 1999;189:1981–6. doi: 10.1084/jem.189.12.1981.PubMedCrossRefGoogle Scholar
  80. 80.
    Robinson BW, Mclemore TL, Crystal RG. Gamma interferon is spontaneously released by alveolar macrophages and lung T lymphocytes in patients with pulmonary sarcoidosis. J Clin Invest. 1985;75:1488–95. doi: 10.1172/JCI111852.PubMedCrossRefGoogle Scholar
  81. 81.
    Fukao T, Satoshi M, Koyasu S. Synergistic effects of IL-4 and IL-18 on IL-12 dependent IFN-γ production by dendritic cells. J Immunol. 2000;164:64–71.PubMedGoogle Scholar
  82. 82.
    Schindler H, Lutz MB, Röllinghoff M, Bogdan C. The production of IFN-γ by IL-12/IL-18-activated macrophages requires STAT4 signaling and is inhibited by IL-4. J Immunol. 2001;166:3075–82.PubMedGoogle Scholar
  83. 83.
    Kambayashi T, Jacob CO, Strassmann G. IL-4 and IL-13 modulate IL-10 release in endotoxin-stimulated murine peritoneal mononuclear phagocytes. Cell Immunol. 1996;171:153–8. doi: 10.1006/cimm.1996.0186.PubMedCrossRefGoogle Scholar
  84. 84.
    Hochrein H, O’keefee M, Luft T, Vandenabeele S, Grumont RJ, Maraskovsky E, et al. Interleukin (IL)-4 is a major regulatory cytokine governing bioactive IL-12 production by mouse and human dendritic cells. J Exp Med. 2000;192:823–33. doi: 10.1084/jem.192.6.823.PubMedCrossRefGoogle Scholar
  85. 85.
    Charalanpos A, Roilides E. Cytokines and fungal infections. J Hematol. 2005;129:583–96.CrossRefGoogle Scholar
  86. 86.
    Romani L. Immunity to fungal infections. Nature Rev Immunol. 2004;4:1–23. doi: 10.1038/nri1255.CrossRefGoogle Scholar
  87. 87.
    Maia DC, Sassá MF, Placeres MC, Carlos IZ. Influence of Th1/Th2 cytokines and nitric oxide in murine systemic infection induced by Sporothrix schenckii. Mycopathologia. 2006;161:11–9. doi: 10.1007/s11046-005-0142-y.PubMedCrossRefGoogle Scholar
  88. 88.
    Tachibana T, Matsuyama T, Mitsuyama M. Involvement of CD4+ T cells and macrophages in acquired protection against infection with Sporothrix schenckii in mice. Med Mycol. 1999;37:397–404. doi: 10.1046/j.1365-280X.1999.00239.x.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Iracilda Zeppone Carlos
    • 1
  • Micheli Fernanda Sassá
    • 1
  • Diana Bridon da Graça Sgarbi
    • 2
  • Marisa Campos Polesi Placeres
    • 1
  • Danielle Cardoso Geraldo Maia
    • 1
  1. 1.Departamento de Análises Clínicas, Faculdade de Ciências Farmacêuticas de Araraquara, Rua Expedicionários do Brasil 1621Universidade Paulista—UNESP, Júlio Mesquita FilhoAraraquaraBrazil
  2. 2.Departamento de Microbiologia e Parasitologia, Instituto BiomédicoUniversidade Federal FluminenseNiteroiBrazil

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