Abstract
The production of prostaglandins (PGs) during fungal infections could be an important suppressor factor of host immune response. Host cells are one source of prostaglandin E2 (PGE2); however another potential source of PGE2 is the fungal pathogen itself. Thus, both host and fungal PGE2 production is theorized to play a role in pathogenesis, being critical for growth of the fungus and to modulate the host immune response. The purpose of this work was to investigate if high and low virulent strains of Paracoccidioides brasiliensis have the capacity to produce PGE2 in vitro, and if this production was related to the fungal growth. The results demonstrated that both strains of P. brasiliensis produce high levels of PGE2 and the treatment with indomethacin, a cyclooxygenase inhibitor, significantly reduced the production of this mediator, as well as the viability of the fungus. Thus, our data indicate that PGE2 is produced by P. brasiliensis by a cyclooxygenase–dependent metabolic pathway, and its production is required for fungal survival. This discovery reveals an important factor that has potentially great implications for understanding the mechanisms of immune deviation during infection.
Similar content being viewed by others
References
Harris SG, Padilha J, Koumas L, Ray D and Phipps RP (2002). Prostaglandins as modulators of immunity. Trends Immunol 23: 144–150
Rocca B and FitzGerald GA (2002). Cyclooxygenases and prostaglandins: shaping up the immune response. Int Immunopharmacol 2: 603–630
Phipps RP, Stein SH and Roper RL (1991). A new view of prostaglandin E regulation of the immune response. Immunol Today 12: 349–352
Betz M and Fox BS (1991). Prostaglandin E2 inhibits production of Th1 lymphokines but not Th2 lymphokines. J Immunol 146: 108–113
Kunkel SL, Spengler M, May MA, Spengler R, Larrick J and Remick D (1988). Prostaglandin E2 regulates macrophage-derived tumor necrosis factor gene expression. J Biol Chem 263: 5380–5384
Matsuoka T, Hirata M, Tanaka H, Takahashi Y, Murata T, Kabashima K, Sugimoto Y, Kobayashi T, Ushikubi F, Aze Y, Eguchi N, Urade Y, Yoshida N, Kimura K, Mizoguchi A, Honda Y, Nagai H and Narumiya S (2000). Prostaglandin D2 as a mediator of allergic asthma. Science 287: 2013–2019
Murphy JW, Zbou A and Wong SC (1997). Direct interaction of human natural killer cells with Cryptococcus neoformans inhibits granulocyte-macrophage colony-stimulating factor and tumor necrosis factor alpha production. Infect Immun 65: 4565–4571
Sergeeva FG, Kalinski P, Wierenga A, Bos JD and Kapsenberg ML (1993). Prostaglandin E2 differentially modulates cytokine secretion profiles of human T helper lymphocytes. J Immunol 150: 5321–5329
Standiford TJ, Kunkel LS, Rolfe MW, Evanolf HL, Allen RM and Strieter RM (1992). Regulation of human alveolar macrophage and blood monocyte-derived interleukin-8 by prostaglandin E2 and dexamethasone. Am J Respir Cell Mol Biol 6: 75–81
Strassmann G, Patil-Koota V, Finkelman F, Fong M and Kambayashi T (1994). Evidence for the involvement of interleukin-10 in the differential deactivation of murine peritoneal macrophages by prostaglandin E2. J Exp Med 180: 2365–2370
Romani L, Kaufmann SH. Immunity to fungi. Research in immunology. Elsevier, Amsterdam, The Netherlands, 1998, 149
Noverr NC, Phare SM, Toews GB, Coffey MJ and Huffnagle GB (2001). Pathogenic yeasts Cryptococcus neoformans and Candida albicans produce immunomodulatory prostaglandins. Infect Immun 69: 2957–2963
Lamacka M and Sajbidor J (1995). The occurrence of prostaglandins and related compounds in lower organisms. Prostaglandins Leukot Essent Fatty Acids 52: 357–364
Franco M, Mendes RP, Moscardi-Bacchi M, Rezkallah-Iwasso MT and Montenegro MR (1989). Paracoccidioidomycosis. Bailliere’s Clin Trop Med Commun Dis 4: 185–220
San-Blás G (1985). Paracoccidioides brasiliensis: cell wall glucans, pathogenicity and dimorphism. Curr Trop Med Mycol 1: 235–257
Brummer E, Castaneda E and Restrepo A (1993). Paracoccidioidomycosis: an update. Clin Microbiol Rev 6: 89–117
Franco M, Montenegro MR, Mendes RP, Marques SA, Dillon NL and Mota NG (1987). Paracoccidioidomycosis: a recently proposed classification of its clinical forms. Rev Soc Bras Med Trop 20: 129–132
Mendes RP (1994). The gamut of clinical manifestations. In: Franco, MF, Lacaz, CS and Restrepo, A (eds) Paracoccidioidomycosis, pp 233–252. CRC Press, , Boca Raton
Giraldo R, Restrepo A, Gutierrez F, Robledo M, Londono F, Fernández H, Sierra F and Calle G (1976). Pathogenesis of paracoccidioidomycosis: a model based on the study of 46 patients. Mycopathologia 58: 63–70
Karhawi AS, Colombo AL and Salomao R (2000). Production of IFN-gamma is impaired in patients with paracoccidioidomycosis during active disease and is restored after clinical remission. Med Mycol 38: 225–229
Benard G, Romano CC, Cacere CR, Juvenale M, Mendes-Giannini MJ and Duarte AJ (2001). Imbalance of IL-2, IFN-gamma and IL-10 secretion in the immunosuppression associated with human paracoccidioidomycosis. Cytokine 13: 248–252
Souto JT, Figueiredo F, Furlaneto A, Pfeffer K, Rossi MA and Silva JS (2000). Interferon-gamma and tumor necrosis factor-alpha determine resistance to Paracoccidioides brasiliensis infection in mice. Am J Pathol 156: 1811–1820
Calvi SA, Peraçoli MTS, Mendes RP, Marcondes-Machado J, Fecchio D, Marques SA and Soares AMVC (2003). Effect of cytokines on the in vitro fungicidal activity of monocytes from paracoccidioidomycosis patients. Microbes Infect 5: 107–113
Carmo JPM, Dias-Melicio LA, Calvi SA, Peraçoli MTS and Soares AMVC (2006). TNF-α activates human monocytes for Paracoccidioides brasiliensis killing by an H2O2-dependent mechanism. Med Mycol 44: 363–368
Arruda C, Franco MF, Kashino SS, Nascimento FR, Fazioli RA, Vaz CA, Russo M and Calich VL (2002). Interleukin-12 protects mice against disseminated infection caused by Paracoccidioides brasiliensis but enhances pulmonary inflammation. Clin Immunol 103: 185–195
Cano LE, Kashino SS, Arruda C, Andre D, Xidieh CF, Singer-Vermes LM, Vaz CA, Burger E and Calich VL (1998). Protective role of gamma interferon in experimental pulmonary paracoccidioidomycosis. Infect Immun 66: 800–806
Kashino SS, Fazioli RA, Cafalli-Favati C, Meloni-Bruneri LH, Vaz CA, Burger E, Singer LM and Calich VL (2000). Resistance to Paracoccidioides brasiliensis infection is linked to a preferential Th1 immune response, whereas susceptibility is associated with absence of IFN-gamma production. J Interferon Cytokine Res 20: 89–97
Baida H, Biselli PJ, Juvenale M, Mendes-Giannini MJ, Duarte AJ and Benard G (1999). Differential antibody isotype expression to the major Paracoccidioides brasiliensis antigen in juvenile and adult form paracoccidioidomycosis. Microbes Infect 1: 273–278
Mamoni RL, Nouer SA, Oliveira SJ, Mussati CC, Rossi CL, Camargo ZP and Blotta MH (2002). Enhanced production of specific IgG4, IgE, IgA and TGF-beta in sera from patients with the juvenile form of paracoccidioidomycosis. Med Mycol 40: 153–159
Mamoni RL, Rossi CL, Camargo ZP and Blotta MH (2001). Capture enzyme-linked immunosorbent assay to detect specific immunoglobulin E in sera of patients with paracoccidioidomycosis. Am J Trop Med Hyg 65: 237–241
Oliveira SJ, Mamoni RL, Musatti CC, Papaiordanou PM and Blotta MH (2002). Cytokines and lymphocyte proliferation in juvenile and adult forms of paracoccidioidomycosis: comparison with infected and non-infected controls. Microbes Infect 4: 139–144
Romano CC, Mendes-Giannini MJS, Duarte AJS and Benard G (2002). IL-12 and neutralization of endogenous IL-10 revert the in vitro antigen-specific cellular immunosupression of paracoccidioidomycosis patients. Cytokine 18: 149–157
Romano CC, Mendes-Giannini MJS, Duarte AJS and Benard G (2005). The role of interleukin-10 in the differential expression of interleukin-12p70 and its beta2 receptor on patients with active or treated paracoccidioidomycosis and healthy infected subjects. Clin Immunol 114: 86–94
Peraçoli MTS, Sugizaki MF, Mendes RP, Naiff R and Montenegro MR (1999). Paracoccidioides brasiliensis isolated from armadillos is virulent to syrian hamsters. Mycopathologia 148: 123–130
Singer-Vermes LM, Ciavaglia MC, Casino SS, Burger E and Calich VLG (1992). The source of the growth-promoting factor(s) affects the plating efficiency of Paracoccidioides brasiliensis. J Med Vet Mycol 30: 261–264
Noverr MC, Toews GB and Huffnagle GB (2002). Production of prostaglandins and leukotrienes by pathogenic fungi. Infect Immun 70: 400–402
Kashino SN, Calich VLG, Burger E and Singer-Vermes LM (1985). In vivo and in vitro characteristics of six Paracoccidioides brasiliensis strains. Mycopathologia 92: 173–178
Zacharias D, Ueda A, Moscardi-Bacchi M, Franco M and San-Blas G (1986). A comparative histopathological, immunological and biochemical study of experimental intravenous paracoccidioidomycosis induced in mice by three Pacoccidioides brasiliensis isolates. J Med Vet Mycol 24: 445–454
Singer-Vermes LM, Burger E, Franco M, Di-Bacchi MM, Mendes-Giannini MJS and Calich VLG (1989). Evaluation of the pathogenicity of seven Paracoccidioides brasiliensis isolates in susceptible inbred mice. J Med Vet Mycol 27: 71–82
Singer-Vermes LM, Burger E, Calich VLG, Modesto-Xavier LH, Sakamoto TN, Sugizaki MF, Meira DA and Mendes RP (1994). Pathogenicity and immunogenicity of Paracoccidioides brasiliensis isolates in the human disease and in an experimental murine model. Clin Exp Immunol 97: 113–119
Silva CL, Alves LMC and Figueiredo F (1994). Involvement of cell wall glucans in the genesis and persistence of the inflammatory reaction caused by the fungus Paracoccidioides brasiliensis. Microbiol 140: 1189–1194
Soares AMVC, Calvi SA, Peraçoli MTS, Fernandez AC, Dias LA and Dos Anjos AR (2001). Modulatory effect of prostaglandins on human monocyte activation for killing of high- and low-virulence strains of Paracoccidioides brasiliensis. Immunol 102: 480–485
Gangopadhyay P, Thadepalli H, Roy I and Ansari A (1979). Identification of species of Candida, Cryptococcus and Torulopsis by gas-liquid chromatography. J Infect Dis 140: 952–958
Marumo K and Aoki Y (1990). Disciminant analysis of cellular fatty acids of Candida species, Torulopsis glabrata and Cryptococcus neoformans determined by gas-liquid chromatography. J Clin Microbiol 28: 1509–1513
Noverr CM and Huffnagle GB (2004). Regulation of Candida albicans morphogenesis by fatty acid metabolites. Infect Immun 72: 6206–6210
Kalo-Klein A and Witkin SS (1990). Prostaglandin E2 enhances and gamma interferon inhibits germ tube formation in Candida albicans. Infect Immun 58: 260–262
Kunkel SL, Spengler M, May MA, Spengler R, Larrick J and Remick D (1988). Prostaglandin E2 regulates macrophage-derived tumor necrosis factor gene expression. J Biol Chem 263: 5380–5384
Sergeeva MG, Gonchar MV, Mevkh AT and Varfolomeyer SD (1997). Prostaglandin E2 biphasic control of lymphocyte proliferation inhibition by picomolar concentrations. FEBS Lett 418: 235–238
Standiford TJ, Kunkel SL, Rolfe MW, Evanoff HL, Allen RM and Strieter RM (1992). Regulation of human alveolar macrophage- and blood monocyte-derived interleukin-8 by prostaglandin E2 and dexamethasone. Am J Respir Cell Mol Biol 6: 75–81
Michelin MA, Figueiredo F and Cunha FQ (2002). Involvement of prostaglandins in the immunosuppression occurring during experimental infection by Paracoccidioides brasiliensis. Exp Parasitol 102: 170–177
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bordon, A.P., Dias-Melicio, L.A., Acorci, M.J. et al. Prostaglandin E2 production by high and low virulent strains of Paracoccidioides brasiliensis . Mycopathologia 163, 129–135 (2007). https://doi.org/10.1007/s11046-007-0098-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11046-007-0098-1