Skip to main content
SpringerLink
Log in

Immune Response Against Sporothrix schenckii in TLR-4-Deficient Mice

Mycopathologia Aims and scope Submit manuscript

Abstract

For many fungal diseases, macrophages are the major cell population implicated in host protection, primarily by their ability to eliminate the invading fungal pathogen through phagocytosis. In sporotrichosis, this remains true, because of macrophages’ ability to recognize Sporothrix schenckii through specific receptors for some of the fungus’ cellular surface constituents. Further confirmation for macrophages’ pivotal role in fungal diseases came with the identification of toll-like receptors, and the subsequent numerous associations found between TLR-4 deficiency and host susceptibility to diverse fungal pathogens. Involvement of TLR-4 in immune response against sporotrichosis has been conducted to investigate how TLR-4 signaling could affect inflammatory response development through evaluation of H2O2 production and IL-1β, IL-6 and TGF-β release during the course of S. schenckii infection on TLR-4-deficient mice. The results showed that macrophages are largely dependent on TLR-4 for inflammatory activation and that in the absence of TLR-4 signaling, increased TGF-β release may be one of the contributing factors for the abrogated inflammatory activation of peritoneal exudate cells during mice sporotrichosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price includes VAT (France)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Freitas DF, do Valle AC, de Almeida Paes R, Bastos FI, Galhardo MC. Zoonotic Sporotrichosis in Rio de Janeiro, Brazil: a protracted epidemic yet to be curbed. Clin Infect Dis. 2010;50(3):453.

    Article  PubMed  Google Scholar 

  2. Ramos-e-Silva M, Vasconcelos C, Carneiro S, Cestari T. Sporotrichosis. Clin Dermatol. 2007;25(2):181–7.

    Article  PubMed  Google Scholar 

  3. Freitas DF, de Siqueira Hoagland B, Do Valle AC, Fraga BB, de Barros MB, de Oliveira Schubach A, de Almeida-Paes R, Cuzzi T, Rosalino CM, Zancopé-Oliveira RM, Gutierrez-Galhardo MC. Sporotrichosis in HIV-infected patients: report of 21 cases of endemic sporotrichosis in Rio de Janeiro, Brazil. Med Mycol. 2011;50(2):170–8.

    Google Scholar 

  4. 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(3):133–6.

    PubMed  CAS  Google Scholar 

  5. Vilela R, Souza GF, Fernandes Cota G, Mendoza L. Cutaneous and meningeal sporotrichosis in a HIV patient. Rev Iberoam Micol. 2007;24(2):161–3.

    Article  PubMed  Google Scholar 

  6. Galhardo MC, Silva MT, Lima MA, Nunes EP, Schettini LE, de Freitas RF, Paes Rde A, Neves Ede S, do Valle AC. Sporothrix schenckii meningitis in AIDS during immune reconstitution syndrome. J Neurol Neurosurg Psychiatry. 2010;81(6):696–9.

    Article  PubMed  Google Scholar 

  7. Oda LM, Kubelka CF, Alviano CS, Travassos LR. Ingestion of yeast forms of Sporothrix schenckii by mouse peritoneal macrophages. Infect Immun. 1983;39(2):497–504.

    PubMed  CAS  Google Scholar 

  8. Penha CV, Bezerra LM. Concanavalin A-binding cell wall antigens of Sporothrix schenckii: a serological study. Med Mycol. 2000;38(1):1–7.

    PubMed  CAS  Google Scholar 

  9. Carlos IZ, Sgarbi DB, Santos GC, Placeres MC. Sporothrix schenckii lipid inhibits macrophage phagocytosis: involvement of nitric oxide and tumour necrosis factor-alpha. Scand J Immunol. 2003;57(3):214–20.

    Article  PubMed  CAS  Google Scholar 

  10. 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.

    Article  PubMed  CAS  Google Scholar 

  11. 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.

    Article  PubMed  CAS  Google Scholar 

  12. Carlos IZ, Sgarbi DB, Placeres MC. Host organism defense by a peptide-polysaccharide extracted from the fungus Sporothrix schenckii. Mycopathologia. 1998–1999;144(1):9–14.

  13. 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(1):11–9.

    Article  PubMed  CAS  Google Scholar 

  14. Medzhitov R. Toll-like receptors and innate immunity. Nat Rev Immunol. 2001;1(2):135–45.

    Article  PubMed  CAS  Google Scholar 

  15. Veerdonk FL, Kullberg BJ, van der Meer JW, Gow NA, Netea MG. Host-microbe interactions: innate pattern recognition of fungal pathogens. Curr Opin Microbiol. 2008;11(4):305–12.

    Article  PubMed  Google Scholar 

  16. Roeder A, Kirschning CJ, Rupec RA, Schaller M, Weindl G, Korting HC. Toll-like receptors as key mediators in innate antifungal immunity. Med Mycol. 2004;42(6):485–98.

    Article  PubMed  CAS  Google Scholar 

  17. Levitz SM. Interactions of toll-like receptors with fungi. Microbes Infect. 2004;6(15):1351–5.

    Article  PubMed  CAS  Google Scholar 

  18. Netea MG, Van der Graaf C, Van der Meer JW, Kullberg BJ. Recognition of fungal pathogens by Toll-like receptors. Eur J Clin Microbiol Infect Dis. 2004;23(9):672–6.

    Article  PubMed  CAS  Google Scholar 

  19. 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):1–10.

    Article  PubMed  CAS  Google Scholar 

  20. 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(2):301–9.

    Article  PubMed  Google Scholar 

  21. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265–75.

    PubMed  CAS  Google Scholar 

  22. Pick E, Mizel D. Rapid microassays for the measurement of superoxide and hydrogen peroxide production by macrophages in culture using an automatic enzyme immunoassay reader. J Immun Methods. 1981;46(2):211–26.

    Article  CAS  Google Scholar 

  23. Kumagai Y, Takeuchi O, Akira S. Pathogen recognition by innate receptors. J Infect Chemother. 2008;14(2):86–92.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  25. Bonfim CV, Mamoni RL, Blotta MH. TLR-2, TLR-4 and dectin-1 expression in human monocytes and neutrophils stimulated by Paracoccidioides brasiliensis. Med Mycol. 2009;47(7):722–33.

    Article  PubMed  CAS  Google Scholar 

  26. Loures FV, Pina A, Felonato M, Araújo EF, Leite KR, Calich VL. Toll-like receptor 4 signaling leads to severe fungal infection associated with enhanced proinflammatory immunity and impaired expansion of regulatory T cells. Infect Immun. 2010;78(3):1078–88.

    Article  PubMed  CAS  Google Scholar 

  27. Weindl G, Naglik JR, Kaesler S, Biedermann T, Hube B, Korting HC, Schaller M. Human epithelial cells establish direct antifungal defense through TLR4-mediated signaling. J Clin Invest. 2007;117(12):3664–72.

    PubMed  CAS  Google Scholar 

  28. Netea MG, Gow NA, Joosten LA, Verschueren I, van der Meer JW, Kullberg BJ. Variable recognition of Candida albicans strains by TLR4 and lectin recognition receptors. Med Mycol. 2010;48(7):897–903.

    Article  PubMed  CAS  Google Scholar 

  29. Pamer EG. TLR polymorphisms and the risk of invasive fungal infections. N Engl J Med. 2008;359(17):1836–8.

    Google Scholar 

  30. Carvalho A, Pasqualotto AC, Pitzurra L, Romani L, Denning DW, Rodrigues F. Polymorphisms in toll-like receptor genes and susceptibility to pulmonary aspergillosis. J Infect Dis. 2008;197(4):618–21.

    Article  PubMed  CAS  Google Scholar 

  31. Ding K, Shibui A, Wang Y, Takamoto M, Matsuguchi T, Sugane K. Impaired recognition by Toll-like receptor 4 is responsible for exacerbated murine Pneumocystis pneumonia. Microbes Infect. 2005;7(2):195–203.

    Article  PubMed  CAS  Google Scholar 

  32. Yauch LE, Mansour MK, Shoham S, Rottman JB, Levitz SM. Involvement of CD14, toll-like receptors 2 and 4, and MyD88 in the host response to the fungal pathogen Cryptococcus neoformans in vivo. Infect Immun. 2004;72(9):5373–82.

    Article  PubMed  CAS  Google Scholar 

  33. Nakamura K, Miyagi K, Koguchi Y, Kinjo Y, Uezu K, Kinjo T, Akamine M, Fujita J, Kawamura I, Mitsuyama M, Adachi Y, Ohno N, Takeda K, Akira S, Miyazato A, Kaku M, Kawakami K. Limited contribution of Toll-like receptor 2 and 4 to the host response to a fungal infectious pathogen. Cryptococcus neoformans. FEMS Immunol Med Microbiol. 2006;47(1):148–54.

    Article  PubMed  CAS  Google Scholar 

  34. Gregory CD, Pound JD. Microenvironmental influences of apoptosis in vivo and in vitro. Apoptosis. 2010;15(9):1029–49.

    Article  PubMed  CAS  Google Scholar 

  35. Miyake K. Roles for accessory molecules in microbial recognition by Toll-like receptors. J Endotoxin Res. 2006;12(4):195–204.

    Article  PubMed  CAS  Google Scholar 

  36. Miyake K. Innate immune sensing of pathogens and danger signals by cell surface toll-like receptors. Semin Immunol. 2007;19(1):3–10.

    Article  PubMed  CAS  Google Scholar 

  37. Lopes-Bezerra LM, Schubach A, Costa RO. Sporothrix schenckii and sporotrichosis. An Acad Bras Cienc. 2006;78(2):293–308.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are grateful to Marisa Campos Polesi Placeres for technical support. This work was supported by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo.

Author information

Authors and Affiliations

  1. Laboratory of Clinical Immunology, School of Pharmaceutical Sciences, São Paulo State University, São Paulo, Brazil

    Micheli Fernanda Sassá, Lucas Souza Ferreira, Livia Carolina de Abreu Ribeiro & Iracilda Zeppone Carlos

Authors
  1. Micheli Fernanda Sassá
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lucas Souza Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Livia Carolina de Abreu Ribeiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Iracilda Zeppone Carlos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Iracilda Zeppone Carlos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sassá, M.F., Ferreira, L.S., de Abreu Ribeiro, L.C. et al. Immune Response Against Sporothrix schenckii in TLR-4-Deficient Mice. Mycopathologia 174, 21–30 (2012). https://doi.org/10.1007/s11046-012-9523-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11046-012-9523-1

Keywords

search

Navigation