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Mycopathologia

, Volume 165, Issue 4–5, pp 209–221 | Cite as

An overview of the immunopathology of human paracoccidioidomycosis

  • Gil Benard
Article

Abstract

We review here the advances in the understanding of the immunopathology of human paracoccidioidomycosis (PCM). Its investigation must take in account the intriguing natural history of the mycosis and its agent, providing clues to the mechanisms that lead to development of disease (unbalanced host–parasite relationship?) or to the clinically silent, chronic carrier state (balanced host–parasite relationship?), in exposed people living in endemic areas. Although the literature on this subject has progressed notably, the overall picture of what are the mechanisms of susceptibility or resistance continues to be fragmentary. Major advances were seen in the description of both the cytokines/chemokines associated to the different outcomes of the host-parasite interaction, and the fungus-monocyte/macrophage interaction, and cytokines released thereof by these cells. However, relatively few studies have attempted to modify, even in vitro, the patients’ unbalanced immune reactivity. Consequently, the benefits of this improved knowledge did not yet reach clinical practice. Fortunately, the previous notion of the immune system as having two nearly independent arms, the innate and adaptive immunities, leaving a large gap between them, is now being overcome. Immunologists are now trying to dissect the connections between these two arms. This will certainly lead to more productive results. Current investigations should address the innate immunity events that trigger the IL-12/IFN-γ axis and confer protection against PCM in those individuals living in endemic areas, who have been infected, but did not develop the mycosis.

Keywords

Paracoccidioidomycosis Paracoccidioides brasiliensis Human immunology Cytokines T-cell Immunesuppression Macrophages 

References

  1. 1.
    Rippon JW. The pathogenic fungi and the pathogenic actinomycetes. 3rd ed. Saunders: Philadelphia; 1988. p. 797.Google Scholar
  2. 2.
    Enarson DA, Rouillon A. The epidemiological basis of tuberculosis control. In: Davies PDO, editors. Clinical tuberculosis. London: Champman & Hall Medical; 1998. p. 35–52.Google Scholar
  3. 3.
    Franco M, Mendes RP, Dillon NL, Mota NGS. Paracoccidioidomycosis, a recently proposed classification of its clinical forms. Rev Soc Bras Med Trop 1987;20: 129–32.PubMedGoogle Scholar
  4. 4.
    Benard G, Neves CP, Gryschek RCB, et al. Severe juvenile type paracoccidioidomycosis in an adult J Med Vet Mycol. 1995;33:67–71.PubMedCrossRefGoogle Scholar
  5. 5.
    Benard G, Franco M. Paracoccidioidomycosis. In: Merz WG, Hay RJ, editors. Topley Wilson’s medical mycology. 10th ed. London: Hodder Arnold; 2005;541–55.Google Scholar
  6. 6.
    Chikamori T, Saka S, Nagano H, et al. Paracoccidioidomycosis in Japan. Report of a case. Rev Inst Med Trop São Paulo 1984;26:267–71.PubMedGoogle Scholar
  7. 7.
    Lacaz CS, Faria JL, Moura RAA. Blastomicose sulamericana associada a moléstia de Hodgkin. Hospital (Rio de Janeiro) 1948;34:313–22.Google Scholar
  8. 8.
    Benard G, Duarte AJS. Paracoccidioidomycosis. A model for evaluation of the effects of human immunodeficiency virus infection on the natural history of endemic tropical diseases. Clin Infect Dis 2000;31:1032–1039.PubMedCrossRefGoogle Scholar
  9. 9.
    Mendes NF, Musatti CC, Leão RC, MendesE, Naspitz CK. Lymphocyte cultures and skin allograft survival in patients with South American Blastomycosis. J Allerg Clin Immunol 1971;48:40–5.Google Scholar
  10. 10.
    Musatti CC, Rezkallah MT, Mendes E, et al. In vivo and in vitro evaluation of cell-mediated immunity in patients with paracoccidioidomycosis. Cell Immunol 1976;24:365–78.PubMedCrossRefGoogle Scholar
  11. 11.
    Mok PWY, Greer DL. Cell-mediated immune responses in patients with paracoccidioidomycosis. Clin Exp Immunol 1977;28:89–98.Google Scholar
  12. 12.
    Restrepo A, Restrepo M, Restrepo F, Aristizábal LH, Moncada LH, Vélez H. Immune responses in paracoccidioidomycosis. A controlled study of 16 patients before and after treatment. Sabouraundia 1978;16:151–63.Google Scholar
  13. 13.
    Arango M, Yazárbal L. T-cell dysfunction and hyperimmunoglobulinemia E in paracoccidioidomycosis. Mycopathologia 1982;79:115–24.PubMedCrossRefGoogle Scholar
  14. 14.
    Costa JC, Pagnano PMG, Bechelli LM, Fiorillo AM, Filho EL. Lymphocyte transformation test in patients with paracoccidioidomycosis. Mycopathologia 1983;84:55–63.PubMedCrossRefGoogle Scholar
  15. 15.
    Mota NGS, Rezkallah IMT, Peraçoli MT et al. Correlation between cell-mediated immunity and clinical forms of paracoccidioidomycosis. Trans R Soc Trop Med Hyg 1985;79:765–71.PubMedCrossRefGoogle Scholar
  16. 16.
    Chequer-Bou-Habib D, Oliveira NMP, Cruz MFF Castro GB. The possible role of circulating immune complexes in the deficiency of cell-mediated immunity in paracoccidioidomycosis. Brazilian J Med Biol Res 1989;2:205–12.Google Scholar
  17. 17.
    Mota NGS, Peraçoli MTS, Mendes RRP, Gattas CR, Marques SA, Soares AMVC, Rezkallah-Iwasso MT. Mononuclear cell subsets in patients with different clinical forms of paracoccidioidomycosis. J Med Vet Mycol 1998;26:105–11.CrossRefGoogle Scholar
  18. 18.
    Moscardi-Bacchi M, Mendes RP, Marques SA et al. In situ localization of T lymphocyte subsets in human paracoccidioidomycosis. J Med Vet Mycol 1989;27:149–58.PubMedCrossRefGoogle Scholar
  19. 19.
    Parise FMR, Marques SA, Soares AMVC, et al. Cytokines released from blood monocytes and expressed in mucocutaneous lesions of patients with paracoccidioidomycosis evaluated before and during trimethoprim-sulfamethoxazole treatment. Br J Dermatol 2006;154:643–50.CrossRefGoogle Scholar
  20. 20.
    Quagliato Jr R, de Capitani EM, Massucio RAC, Rezende SM, Balthazar AB. The association of paracoccidioidomycosis with tuberculosis. Rev Inst Med Trop São Paulo 2005;47(suppl.):37, abstract#05.07.Google Scholar
  21. 21.
    Benard G, Hong MA, Negro GMBD, Batista L, Shikanai-Yasuda MA, Duarte AJS. Antigen-specific immunosuppression in paracoccidioidomycosis. Am J Trop Med. Hyg 1996;54:7–12.PubMedGoogle Scholar
  22. 22.
    Benard G, Mendes-Giannin MJS, Juvenale M, et al. Immunosuppression in paracoccidioidomycosis. T cell hyporesponsiveness to two Paracoccidioides brasiliensis glycoproteins that elicit strong humoral immune response. J Infect Dis 1997;175:1263–67.PubMedGoogle Scholar
  23. 23.
    Sugizaki MF, Peraçoli MTS, Mendes-Giannini MJS, Soares AMVC, Kurokawa CS, Mendes RP, Marques SA, Maia DVF. Correlation between antigenemia of Paracoccidioides brasiliensis, inhibiting effects of plasma in patients with paracoccidioidomycosis. Med Mycol 1999;37:277–84.PubMedCrossRefGoogle Scholar
  24. 24.
    Diniz SN, Cisalpino PS, Koury MC, Andrade GMQ, Nogueira MGS, Goes AM. In vitro human immune reactivity of fast protein liquid chromatography fractionated Paracoccidioides brasiliensis soluble antigens. Microbes Infect 1999;1:53–360.CrossRefGoogle Scholar
  25. 25.
    Oliveira SJ, Mamoni RL, Musatti CC, et al. Cytokines and lymphocyte proliferation in juvenile and adult forms of paracoccidioidomycosis. Comparison with infected and non-infected controls. Microbes Infect 2002;4:139–44.PubMedCrossRefGoogle Scholar
  26. 26.
    Campanelli AP, Martins GA, Souto JT, et al. Fas-Fas Ligand (CD95-CD95L) and cytotoxic T lymphocyte antigen-4 engagement mediate T cell unresponsiveness in patients with paracoccidoidomycosis. J Infect Dis 2003;187:505–1496.CrossRefGoogle Scholar
  27. 27.
    Karhawi AS, Colombo AL, Salomão R. Production of IFN-gamma is impaired in patients with paracoccidioidomycosis during active disease and is restored after clinical remission Med Mycol 2000;38:225–9.Google Scholar
  28. 28.
    Benard G, Romano CC, Cacere CR. et al. Imbalance of IL-2, IFN-gamma and IL-10 secretion in the immunosuppression associated with human paracoccidioidomycosis. Cytokine 2001;13:248–52.PubMedCrossRefGoogle Scholar
  29. 29.
    Mello LM, Vergara MLS, Rodrigues Júnior V. Patients with active infection with Paracoccidioides brasiliensis immune response characterized by high interleukin 4 and interleukin 5 production. Hum Immunol 2002;63:149–54.CrossRefGoogle Scholar
  30. 30.
    Fornazim MC, Balthazar A, Quagliato R Jr et al. Evaluation of bronchoalveolar cells in pulmonary paracoccidio idomycosis. Eur Respir J 2003;22:895–9.PubMedGoogle Scholar
  31. 31.
    Calvi SA, Soares AM, Peraçoli MT, Mendes RP, et al. Effect of cytokines on the in vitro fungicidal activity of monocytes from paracoccidioidomycosis patients. Microbes Infect. 2003;5:107–13.PubMedCrossRefGoogle Scholar
  32. 32.
    Peraçoli MT, Kurokawa CS, Calvi SA, et al. Production of pro-and anti-inflammatory cytokines by monocytes from patients with paracoccidioidomycosis. Microbes Infect 2003;5:8–13.CrossRefGoogle Scholar
  33. 33.
    Mamoni RL, Blotta MHSL. Kinetics of citokines and chemokines gene expression distinguishes Paracoccidioides brasiliensis infection from disease. Cytokine 2005;32:20–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Mamoni RL, Blotta MHSL. Flow-cytometric analysis of cytokine production in human paracoccidiodomycosis. Cytokine 2006;35:207–16.PubMedCrossRefGoogle Scholar
  35. 35.
    Ferreira KS, Almeida SR Immunization of susceptible mice with gp43-pulsed dendritic cells induces an increase of pulmonary Paracoccidioidomycosis. Immunol Lett 2006;103:121–6.PubMedCrossRefGoogle Scholar
  36. 36.
    Franco M. Host-parasite relationships in paracoccioidomycosis. J Med Vet Mycol 1986;25:5–18.CrossRefGoogle Scholar
  37. 37.
    Sandoval MBT Sotto MN, de Brito T. Antigen distribution in mucocutaneous biopsies of human paracoccidioidomycosis. Int J Surg Pathol 1996;3:181–8.Google Scholar
  38. 38.
    Neworal EPM, Altemani A Mamoni RL, Noronha IL, Blotta MHSL. Immunocytochemical localization of cytokines and inducible nitric oxide synthase (INOS) in oral mucosa and lymph nodes of patients with paracoccidiodomycosis. Cytokine 2003;21:234–41.PubMedCrossRefGoogle Scholar
  39. 39.
    Pagliari C, Sotto MN, et al. Dendritic cells and pattern of cytokines in paracoccidioidomycosis skin lesions. Am J Dermatopathol 2003;25:107–12.PubMedCrossRefGoogle Scholar
  40. 40.
    Burger E, Vaz CC, Sano A, Calich VL, Singer LMV, Xidiel CF, Kashima SS, Nishimura K, Miyaji M. Paracoccidioides brasiliensis infection in nude mice: studies with isolates differing in virulence and definition of their T cell-dependent and T cell independent components. Am J Trop Med Hyg 1996;55:8–391.Google Scholar
  41. 41.
    Kurita N, Oarada M, Brummer E, et al. Fungicidal activity of human peripheral blood leukocytes Paracoccidioides brasiliensis yeast cells. Med Mycol 2005;43:22–417.CrossRefGoogle Scholar
  42. 42.
    Kurita N, Oarada M, Miyaji M, et al. Effect of cytokines on antifungal activity of human polymorphonuclear leucocytes against yeast cells of Paracoccidioides brasiliensis Med Mycol 2000;38:177–82.PubMedCrossRefGoogle Scholar
  43. 43.
    Rodriguez DR, Dias MLA, Calvi SA, Peracoli MT, Soares AM. Paracoccidioides brasilienses killing by IFN-gamma, TNF-alpha and GM-CSF activated human neutrophils: role for oxygen metabolites. Med Mycol 2007;45:27–33.CrossRefGoogle Scholar
  44. 44.
    Goihman-Yahr M, Albornoz MC, Yarzábal L, Gómez MH, Martín BS, Ocanto A, Gil F, Convit J. Defect of in vitro digestive ability of polymorphonuclear leukocytes in paracoccidioidomycosis. Infect Immun, 1980;48:557–66.Google Scholar
  45. 45.
    Corvino CL, Mamoni RL, Fagundes GZ, Blotta MH. Serum interleukin 18 and soluble tumor necrosis factor receptor 2 are associated with disease severity in patients with paracoccidioidomycosis. Clin Exp Immunol 2007;147:90–483.Google Scholar
  46. 46.
    Soares AMVC, Calvi SA, Peraçoli MTS, Fernandez AC, Dias LA, Anjos AR. Modulatory effect of prostaglandins on human monocyte activation for killing of high and low virulence strains of Paracoccidioides brasiliensis. Immunology 2001;102:480–5.PubMedCrossRefGoogle Scholar
  47. 47.
    Carmo JPM, Dias MLA, Calvi SA, Peraçoli MTS, Soares AMVC. TNF-α activates human monocytes for Paracoccidioides brasiliensis killing by an H2O2 dependent mechanism. Med Mycol 2006;44:363–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Bannwart CF. Efeito da interleucina-15 sobre a atividade fungicida, metabolismo oxidativo e produção de citocina por monócitos humanos, infectados in vitro com Paracoccidioides brasiliensis. MsC thesis, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista “Júlio de Mesquita Filho” Botucatu, 2007.Google Scholar
  49. 49.
    Dias MLA, Calvi SA, Peracoli MT, Soares AMVC. Inhibitory effect of deferoxamine on Paracoccidioides brasiliensis survival in human monocytes: reversal by holotransferin but not by apotransferrin. Rev Inst Med Trop São Paulo 2005;47:263–6.Google Scholar
  50. 50.
    Fornari MC, Bava AJ, Guereno MT, Berardi VE, Silaf MR, Negroni R, Diez RA. High serum interleukin-10 and tumor necrosis factor alpha levels in chronic paracoccidioidomycosis. Clin Diag Lab Immunol 2001;8:1036–8.CrossRefGoogle Scholar
  51. 51.
    Nascimento FR,Calich VL, Rodriguez D, Russo M. Dual role for nitric oxide in paracoccidioidomycosis: essential for resistance, but overproduction associated with susceptibility. J Immunol 2002;1684:593–600.Google Scholar
  52. 52.
    Romano CC, Mendes GMJS, Duarte AJS, Benard G, Mendes-Giannini MJS, Duarte AJS. IL-12 and neutralization of endogenous IL-10 revert the in vitro antigen-specific cellular immunosuppression of paracoccidioidomycosis patients. Cytokine 2002;18:57–149.CrossRefGoogle Scholar
  53. 53.
    Souto JT, Figueiredo F, Furlanetto A, Pfeffer K, et al. Interferon-gamma and tumor necrosis factor alpha determine resistance to Paracoccidioides brasiliensis infection in mice. Am J Pathol 2000;156:20–1811.Google Scholar
  54. 54.
    Romano CC, Mendes GMJ, Duarte AJS, Benard G, et al. The role of interleukin-10 in the differential expression of interleukin-12p70 and its beta-2 receptor on patients with active or treated paracoccidioidomycosis and healthy infected subjects Clin Immunol. 2005;114:86–94.Google Scholar
  55. 55.
    Vasconcelos DM, Grumach AS, Yamaguti A, Andrade MEB, Fieschi C, Beaucoudre L, Casanova JL, Duarte AJS. Paracoccidioides brasiliensis disseminated disease in a patient with inherited deficiency in the β1 subunit of the Interleukin (IL)-12/IL23 receptor. Clin Inf Dis 2005;41:31–7.CrossRefGoogle Scholar
  56. 56.
    Soares AMVC, Silva WB, Rodrigues DR, Calvi SA, Peraçoli MTS, Kurokawa CS. IL-10 but not TGF-beta inhibits Paracoccidioides brasilensis killing by human activated monocytes. Ann Rev Biomed Sci- Special Issue 2002;4:89.Google Scholar
  57. 57.
    Soares AMVC, Carmo JP, Peraçoli MTS S A, Dias LA, Tavian EG. Role of granulocyte macrophage colony simulating factor (GM-CSF) on human monocytes activation in vitro for high virulent Pacoccidioides brasiliensis killing. Ann Rev Biomed Sci- Special Issue 2002;4:94.Google Scholar
  58. 58.
    Bacchi MM, Brummer E Stevens DA. Support of Paracoccidioides brasiliensis multiplication by human mono cytes or macrophages: inhibition by activated phagocytes. J Med Microbiol 1994;40:159–64.CrossRefGoogle Scholar
  59. 59.
    Chen W, Hershey GKKH. Signal transducer and activator of transcription signals in allergic disease. J Allergy Clin Immunol 2007;119:529–41.PubMedCrossRefGoogle Scholar
  60. 60.
    Levy DE, Darnell Jr JE. Transcriptional control and biological impact. Nat Rev Mol Cell Biol 2002;3:651–62.PubMedCrossRefGoogle Scholar
  61. 61.
    Lang R. Tunning of macrophage responses by STAT3-inducing cytokines: molecular mechanisms and consequences in infection. Immunobiology 2005;210:63–76.PubMedCrossRefGoogle Scholar
  62. 62.
    Shea JJO, Park H, Pesu M, Borie D, Changelian P. New strategies for immunosuppression: interfering with cytokines by targeting the Jak/Stat pathway. Cur Opin Rheumatol 200;17:305–11.Google Scholar
  63. 63.
    Popescu FD. New asthma drugs acting on gene expression. J Cell Mol Med 2003;7:475–86.PubMedCrossRefGoogle Scholar
  64. 64.
    Chen LW. Co-signaling molecules of the B7- CD28 family in positive and negative regulation of T lymphocytes response. Microbes Infect 2004;6:759–66.PubMedCrossRefGoogle Scholar
  65. 65.
    Marth T, Strober W, Kelsall BL. High dose tolerance in ovalbumine TCR-transgenic mice. Systemic neutralization of IL-12 augments TGF-β secretion and T cell apoptosis. J Immunol 1996;157:2348–57.PubMedGoogle Scholar
  66. 66.
    Cacere CR, Romano CC, Mendes-Giannini MJS, Duarte AJS, Benard G. The role of apoptosis in the antigen-specific T-cell hyporesponsiveness of paracoccidioidomycosis patients. Clin Immunol 2002;105:215–22.PubMedCrossRefGoogle Scholar
  67. 67.
    Cavassani KA, Campanelli AP, Moreira AP et al. Systemic and local characterization of regulatory T cells in a chronic fungal infection in humans. J Immunol 2006;177:5811–8.PubMedGoogle Scholar
  68. 68.
    Cavassani KA. Participação de células TCD4CD25 regulatórias (Tregs) no controle da resposta imune durante a paracoccidioidomicose humana. PhD Thesis, Faculdade de Medicina de Ribeirão Preto, University of São Paulo, Brazil, 2006.Google Scholar
  69. 69.
    Von Boehmer H. Mechanisms of suppression by suppressor T cells. Nat Immunol 2005;6:44–338.CrossRefGoogle Scholar
  70. 70.
    Freeman GJ, Long AJ, Bourque Y, Chernova T, et al. Engagement of the PD-1 immunoinhibitor receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 2000;192:1027–34.PubMedCrossRefGoogle Scholar
  71. 71.
    Taborda CP, Juliano MA, Puccia R, Franco M, Travassos LR. Mapping of the T-cell epitope in the major 43 kilodalton glycoprotein of Paracoccidioides brasilliensis which induces a Th-1 response protective against fungal infection in Balb/c mice. Infect Immun 1998;66:786–93.PubMedGoogle Scholar
  72. 72.
    Iwai LK, Yoshida M, Shikanai-Yasuda MA, Goldberg AC, Juliano MA, Juliani L, Sette A, Kalil J, Cunha NE, Travassos LR. In silico prediction of peptides binding to multiple HLA-DR molecules accurately identifies immunodominant epitopes from gp43 of Paracoccidioides brasiliensis frequently recognized in primary peripheral blood mononuclear cell responses from sensitized individuals. Mol Med 2003;9:19–209.Google Scholar
  73. 73.
    Iwai LK, Yoshida M, Sadahiro A, Marin LM, Goldberg AC, Juliano MA, Juliano L, Shikanai-Yasuda MA, Kalil J, Neto EC, Travassos LR. T-Cell recognition of Paracocciodioides brasiliensis GP43-derived peptides in patients with paracoccidioidomycosis and healthy individuals. Clin Vac Immunol 2007;14:474–6.Google Scholar
  74. 74.
    Sadahiro AS, Diogo CL, Oshiro TM, Shikanai-Yasuda MA. Kinetics of IFN-gamma, TNF-alpha, IL-10 and IL-4 production by mononuclear cells stimulated with gp43 peptides, in patients cured of paracoccidioidomycosis. Rev Soc Bras Med Trop 2007;40:156–62.PubMedCrossRefGoogle Scholar
  75. 75.
    Restrepo FM, Restrepo M, Restrepo A. Blood groups and HLA antigens in paracoccidioidomycosis. Sabouraudia 1983;21:35–9.PubMedGoogle Scholar
  76. 76.
    Lacerda GB, Arce GB, Telles Filho FQ. Increased frequency of HLA-B40 in patients with paracoccidioidomycosis. J Med Vet Mycol 1988;26:253–256.PubMedCrossRefGoogle Scholar
  77. 77.
    Goldani LZ, Monteiro CM, Donadi EA, Martinez R, Voltarelli JC. HLA antigens in Brazilian patients with paracoccidioidomycosis. Mycopathologia 1991;114:89–91.PubMedCrossRefGoogle Scholar
  78. 78.
    Rebellato CLK. Estudo da associação entre antígenos HLA-A, B, C, DR e DQ e a paracoccidiodomicose infecção e a forma crônica da paracoccidioidomicose doença. PhD thesis, Universidade Federal do Paraná, 1996.Google Scholar
  79. 79.
    Dias MF, Pereira AC, Pereira A, Alves MS. The role of HLA antigens in the development of paracoccidioidomycosis. J Eur Acad Dermatol Venereol 2000;14:166–71.PubMedCrossRefGoogle Scholar
  80. 80.
    Sadahiro A, Roque AC, Shikanai YMA. Generic human leukocyte antigen class II (DRB1 and QB1) alleles in patients with paracoccidioidomycosis. Med Mycol 2007;45:35–40.PubMedCrossRefGoogle Scholar
  81. 81.
    Bozzi A, Pereira PPN, Reis BS, Goulart MI, Pereira MCN, Pedroso EP, Leite MF, Goes AM. Interleukin––10 and tumor necrosis factor-α single nucleotide gene polymorphism frequency in paracoccidioidomycosis. Hum Immunol, 2006;67:931–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Tobon AM, Agudelo CA, Osorio ML, Alvarez DI, Arango M, Cano LE, Restrepo A. Residual pulmonary abnormalities in adult patients with chronic paracoccodioidomycosis prolonged follow up after itraconazole therapy. Clin Infect Dis 2003;7:898–904.CrossRefGoogle Scholar
  83. 83.
    Jouanguy E, Cherradi SL, Fondanèche MC, Tuerlinckx D, Blanche S, Emile JF, Gaillard JL, Schreiber R Levin M, Fischer A Hivroz C, Casanova JL. Partial Interferon-γ receptor 1 deficiency in a child with tuberculoid bacillus Calmette-Guérin infection and a sibling with clinical tuberculosis. J Clin Invest 1997;11:2658–64.CrossRefGoogle Scholar
  84. 84.
    Akahoshi M, Nakashima H, Miyake K, InoueY, Shimizu S, TanakaY, Okada K, Otsuka T, Harada M. Influence of interleukin-12 receptor beta l polymorphisms on tuberculosis. Hum Genet 2003;12:43–237.Google Scholar
  85. 85.
    Campos MCRM, Gesztesi JL, Vincentini AP, Lopes JD, Camargo ZP. Expression aond isoforms of GP43 in different strains of Paracoccidioides brasilensis. J Med Vet Mycol 1995;33:223–7.PubMedCrossRefGoogle Scholar
  86. 86.
    Barbosa HF, Montenegro MR, Bagagli E. Virulence profiles of ten Paracoccidioides brasilensis isolates obtained from armadillos (Dasypus novemcinctus). Med Mycol 2003;41:89–96.CrossRefGoogle Scholar
  87. 87.
    Carvalho KC, Ganiko LBWL, Morais FV, Marques ER, Goldman GH, Franco MF, Puccia R. Virulence of paracoccioidioides brasiliensis and GP43 expression in isolates bearing known PbGP43 genotype. Microbes Infect 2005;7:55–65.PubMedCrossRefGoogle Scholar
  88. 88.
    Kurokawa CS, Lopes CR, Sugizaki MF, Kuramae EE, Franco MF Peraçoli MTS. Virulence profile of ten Paracoccidioides brasiliensis isolates. Association with morphologic and genetic patterns. Rev Inst Med Trop S Paulo 2005, 47:257–62.PubMedCrossRefGoogle Scholar
  89. 89.
    Zacharias D, Ueda A, Moscardi BM, Franco M, San BG. A comparative histopathological, immunological, and biochemical study of experimental intravenous paracoccidioidomycosis induced in mice by three Paracoccidioides brasiliensis isolates. J Med Vet Mycol 1986;24:445–54.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  1. 1.Laboratory of Dermatology and Immunodeficiencies (LIM-56)Medical School of the University of São PauloSao PauloBrazil

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