Involvement of Major Components from Sporothrix schenckii Cell Wall in the Caspase-1 Activation, Nitric Oxide and Cytokines Production During Experimental Sporotrichosis

Abstract

Sporotrichosis is a chronic infection caused by the dimorphic fungus Sporothrix schenckii, involving all layers of skin and the subcutaneous tissue. The role of innate immune toll-like receptors 2 and 4 in the defense against this fungus has been reported, but so far, there were no studies on the effect of cell wall major components over the cytosolic oligo-merization domain (NOD)-like receptors, important regulators of inflammation and responsible for the maturation of IL-1β and IL-18, whose functions are dependents of the caspase-1 activation, that can participate of inflammasome. It was evaluated the percentage of activation of caspase-1, the production of IL-1β, IL-18, IL-17, IFN-γ and nitric oxide in a Balb/c model of S. schenckii infection. It was observed a decreased activity of caspase-1 during the fourth and sixth weeks of infection accompanied by reduced secretion of the cytokines IL-1β, IL-18 and IL-17 and high production of nitric oxide. IFN-γ levels were elevated during the entire time course of infection. This temporal reduction in caspase-1 activity coincides exactly with the reported period of fungal burden associated with a transitory immunosuppression induced by this fungus and detected in similar infection models. These results indicate the importance of interaction between caspase-1, cytokines IL-1β and IL-18 in the host defense against S. schenckii infection, suggesting a participation the inflammasome in this response.

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Abbreviations

EL:

Lipid extract

F1:

Alkali-insoluble fraction

NO:

Nitric oxide

BHI:

Brain heart infusion

PBS:

Phosphate-buffered saline

PECs:

Peritoneal exudate cells

LPS:

Lipopolysaccharide

ELISA:

Enzyme-linked immunosorbent assay

ConA:

Concanavalin A

FLICA:

Carboxyfluorescein

IL:

Interleukin

PRR:

Pattern recognition receptors

NLRs:

NOD-like receptors

PAMP:

Pathogen-associated molecular patterns

ASC:

Protein associated with apoptosis

References

  1. 1.

    Marimon R, Cano J, Gene J, Sutton DA, Kawasaki M, Guarro J. Sporothrix brasiliensis, S. globosa, and S. mexicana, three new Sporothrix species of clinical interest. J Clin Microbiol. 2007;45:3198–206.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  2. 2.

    Messias AR, de Hoog S, Camargo ZP. Emergence of pathogenicity in the Sporothrix schenckii complex. Med Mycol. 2013;51:405–12.

    Article  Google Scholar 

  3. 3.

    Romeo O, Criseo G. What lies beyond genetic diversity in Sporothrix schenckii species complex? New insights into virulence profiles, immunogenicity and protein secretion in S. schenckii sensu stricto isolates. Virulence. 2013;4(3):1–4.

    Article  Google Scholar 

  4. 4.

    Evangelista MMO, Almeida-Paes R, Gutierrez-Galhardo MC, Zancope-Oliveira RM. Molecular identification of the Sporothrix schenckii complex. Rev Iberoam Micol. 2014;31(1):2–6.

    Article  Google Scholar 

  5. 5.

    Espinoza-Hernándes CJ, Jesús-Silva A, Toussaint-Caire S, Arenas R. Disseminated sporotrichosis with cutaneous and testicular involvement. Actas Dermosifiliogr. 2014;105(2):204–6.

    Article  Google Scholar 

  6. 6.

    La Hoz RM, Baddley JW. Subcutaneous fungal infections. Curr Infect Dis Rep. 2012;14:530–9.

    PubMed  Article  Google Scholar 

  7. 7.

    Barros MBL, Almeida-Paes R, Schubach O. Sporothrix schenckii and sporotrichosis. Clin Microbiol Rev. 2011;24:633–54.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  8. 8.

    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(3):139–44.

    CAS  PubMed  Article  Google Scholar 

  9. 9.

    Carlos IZ, Zini MM, Sgarbi DB, Angluster J, Alviano CS, Silva CL. Disturbances in the production of interleukin 1 and tumor necrosis factor in disseminated murine sporotrichosis. Mycopathologia. 1994;127(3):189–94.

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Carlos IZ, Sgarbi BD, Placeres MC. Host organism defense by a peptide polysaccharide extracted from the fungus Sporothrix schenckii. Mycopathologia. 1999;144(1):9–14.

    CAS  Article  Google Scholar 

  11. 11.

    Carlos IZ, Sassá MF, da Graça Sgarbi DB, Placeres MC, Maia DC. Current research on the immune response to experimental sporotrichosis. Mycopathologia. 2009;168:1–10.

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Alba-Fierro CA, Pérez-Torres A, López-Romero E, Cuéllar-Cruz M, Ruiz-Baca E. Cell wall proteins of Sporothrix schenckii as immunoprotective agents. Rev Iberoam Micol. 2014;31(1):86–9.

    PubMed  Article  Google Scholar 

  13. 13.

    Sassá MF, Saturi AE, Souza LF, Ribeiro LC, Sgarbi DB, Carlos IZ. Response of macrophage Toll-like receptor 4 to a Sporothrix schenckii lipid extract during experimental sporotrichosis. Immunology. 2009;128:301–9.

    PubMed Central  PubMed  Article  Google Scholar 

  14. 14.

    Sassá MF, Ferreira LS, Ribeiro LC, Carlos IZ. Immune response against Sporothrix schenckii in TLR-4-deficient mice. Mycopathologia. 2012;174:21–30.

    PubMed  Article  Google Scholar 

  15. 15.

    Negrini TC, Ferreira LS, Alegranci P, Arthur RA, Sundfeld PP, Maia DC, Spolidorio LC, Carlos IZ. Role of TLR-2 and fungal surface antigens on innate immune response against Sporothrix schenckii. Immunol Invest. 2013;42:36–48.

    CAS  Article  Google Scholar 

  16. 16.

    Negrini TC, Ferreira LS, Arthur RA, Alegranci P, Placeres MCP, Spolidorio LC, Carlos IZ. Influence of TLR-2 in the immune response in the infection induced by fungus Sporothrix schenckii Immunol Invest. 2014; doi:10.3109/08820139.2013.879174.

  17. 17.

    Kumar H, Kawai T, Akira S. Pathogen recognition by the innate immune system. Int Rev Immunol. 2011;30(1):16–34.

    CAS  PubMed  Article  Google Scholar 

  18. 18.

    Kim JJ, Jo EK. NLRP3 Inflammasome and host protection against bacterial infection. J Korean Med Sci. 2013;28:1415–23.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  19. 19.

    Sollberger G, Strittmatter GE, Garstkiewicz M, Sand J, Beer HD. Caspase-1: the inflammasome and beyond. Innate Immun. 2014;20(2):115–25.

    PubMed  Article  Google Scholar 

  20. 20.

    Veerdonk FL, Netea MG, Dinarello CA, Joonsten LA. Inflammasome activation and IL-1β and IL-18 processing during infection. Trends Immunol. 2011;32:110–6.

    PubMed  Article  Google Scholar 

  21. 21.

    Hise AG, Tomalka J, Ganesan S, Patel K, Hall BA, Brown GD, Fitzgerald KA. An essential role for the NLRP3 inflammasome in host defense against the human fungal pathogen Candida albicans. Cell Host Microbe. 2009;5:487–97.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  22. 22.

    Fernandes KS, Neto EH, Brito MM, Silva JS, Cunha FQ, Barja-Fidalgo C. Detrimental role of endogenous nitric oxide in host defence against Sporothrix schenckii. Immunology. 2008;123:469–79.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  23. 23.

    Niedbala W, Besnard AG, Jiang HR, Alves-Filho JC, Fukada SY, Nascimento D, Mitani A, Pushparaj P, Alqahtani MH, Liew FY. Nitric oxide-induced regulatory T cells inhibit Th17 but not Th1 cell differentiation and function. J Immunol. 2013;191(1):164–70.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  24. 24.

    Kanetsuna F, Carbonell LM, Moreno RE, Rodrigues J. Cell wall composition of the yeast and mycelial forms of Paracoccidioides brasiliensis. J Bacteriol. 1969;97:1036–41.

    CAS  PubMed Central  PubMed  Google Scholar 

  25. 25.

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

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Díaz-Jiménez DF, Pérez-García LA, Martínez-Álvarez JA, Mora-Montes HM. Role of the fungal cell wall in pathogenesis and antifungal resistance. Curr Fungal Infect Rep. 2012;6:275–82.

    Article  Google Scholar 

  27. 27.

    Maia DC, Sassa 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.

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Carlos IZ, Sgarbi DBG, Santos GC, Placeres MCP. Sporothrix schenckii lipid inhibits macrophage fagocytosis: involvement of nitric oxide and tumour necrosis factor-α. Scand J Immunol. 2003;57:214–20.

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Chen G, Pedra JH. The inflammasome in host defense. Sensors. 2010;10(1):97–111.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  30. 30.

    Romani L. Immunity to fungal infections. Nat Rev Immunol. 2011;11:275–88.

    CAS  PubMed  Article  Google Scholar 

  31. 31.

    Dinarello CA. Blocking IL-1 in systemic inflammation. J Exp Med. 2005;201(9):1355–9.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  32. 32.

    Sahoo M, Ceballos-Olvera I, Barrio L, Re F. Role of the inflammasome, IL-1β, and IL-18 in bacterial infections. Sci World J. 2011;11:2037–50.

    CAS  Article  Google Scholar 

  33. 33.

    Keyel PA. How is inflammation initiated? Individual influences of IL-1, IL-18 and HMGB1. Cytokine. 2014;69(1):136–45.

    CAS  PubMed  Article  Google Scholar 

  34. 34.

    Huang W, Na L, Fidel PL, Schwarzenberger P. Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice. J Infect Dis. 2004;190:624–31.

    CAS  PubMed  Article  Google Scholar 

  35. 35.

    Gonzales A, de Gregori W, Velez D, Restrepo A, Cano LE. Nitric oxide participation in the fungicidal mechanism of gamma interferon-activated murine macrophages against Paracoccidioides brasiliensis conidia. Infect Immun. 2000;68(5):2546–52.

    Article  Google Scholar 

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Acknowledgments

The authors are grateful to Marisa Campos Polesi Placeres for technical support. This work was supported by grants from the State of Sao Paulo Research Foundation (FAPESP) (Grants No. 2013/03190-5), National Council of Scientific and Technological Development (CNPQ) and Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior (CAPES, Brazil) and Foreigner Visiting Professor Program (Grant 07610130).

Ethical standard

The authors declare that the experiments comply with the laws in force in the country in which they were performed.

Conflict of interest

The authors declare that there is no conflict of interest.

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Correspondence to Iracilda Zeppone Carlos.

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Gonçalves, A.C., Maia, D.C.G., Ferreira, L.S. et al. Involvement of Major Components from Sporothrix schenckii Cell Wall in the Caspase-1 Activation, Nitric Oxide and Cytokines Production During Experimental Sporotrichosis. Mycopathologia 179, 21–30 (2015). https://doi.org/10.1007/s11046-014-9810-0

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Keywords

  • Cytokines
  • Caspase-1
  • Nitric oxide
  • Sporothrix schenckii