Skip to main content

Dendritic Cell-Based Vaccine Against Fungal Infection

  • Protocol
  • First Online:
Vaccine Design

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1403))

Abstract

Several pathogenic fungi, including Cryptococcus gattii, Histoplasma capsulatum, Coccidioides immitis, and Penicillium marneffei, cause serious infectious diseases in immunocompetent humans. However, currently, prophylactic and therapeutic vaccines are not clinically used. In particular, C. gattii is an emerging pathogen and thus far protective immunity against this pathogen has not been well characterized. Experimental vaccines such as component and attenuated live vaccines have been used as tools to study protective immunity against fungal infection. Recently, we developed a dendritic cell (DC)-based vaccine to study protective immunity against pulmonary infection by highly virulent C. gattii strain R265 that was clinically isolated from bronchial washings of infected patients during the Vancouver Island outbreak. In this approach, bone marrow-derived DCs (BMDCs) are pulsed with heat-killed C. gattii and then transferred into mice prior to intratracheal infection. This DC vaccine significantly increases interleukin 17A (IL-17A)-, interferon gamma (IFN-γ)-, and tumor necrosis factor alpha (TNF-α)-producing T cells in the lungs and spleen and ameliorates the pathology, fungal burden, and mortality following C. gattii infection. This approach may result in the development of a new means of controlling lethal fungal infections. In this chapter, we describe the procedures of DC vaccine preparation and murine pulmonary infection model for analysis of immune response against C. gattii.

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

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Chen S, Sorrell T, Nimmo G et al (2000) Epidemiology and host- and variety-dependent characteristics of infection due to Cryptococcus neoformans in Australia and New Zealand. Australasian Cryptococcal Study Group. Clin Infect Dis 31:499–508

    Article  CAS  PubMed  Google Scholar 

  2. Galanis E, MacDougall L, Kidd S et al (2010) Epidemiology of Cryptococcus gattii, British Columbia, Canada, 1999–2007. Emerg Infect Dis 16:251–257

    Article  PubMed  PubMed Central  Google Scholar 

  3. Smith RM, Mba-Jonas A, Tourdjman M et al (2014) Treatment and outcomes among patients with Cryptococcus gattii infections in the United States Pacific Northwest. PLoS One 9, e88875

    Article  PubMed  PubMed Central  Google Scholar 

  4. Lizarazo J, Escandón P, Agudelo CI et al (2014) Retrospective study of the epidemiology and clinical manifestations of Cryptococcus gattii infections in Colombia from 1997–2011. PLoS Negl Trop Dis 8, e3272

    Article  PubMed  PubMed Central  Google Scholar 

  5. BCCDC (2011) Environmental pathogens, Cryptococcus gattii. British Columbia annual summary of reportable diseases 2011, pp 112–113

    Google Scholar 

  6. CDC (2010) Emergence of Cryptococcus gattii, Pacific Northwest, 2004–2010. Morb Mortal Wkly Rep 59:865–868

    Google Scholar 

  7. Ngamskulrungroj P, Chang Y, Sionov E, Kwon-Chung KJ (2012) The primary target organ of Cryptococcus gattii is different from that of Cryptococcus neoformans in a murine model. mBio 3:e00103–e00112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Okubo Y, Wakayama M, Ohno H et al (2013) Histopathological study of murine pulmonary cryptococcosis induced by Cryptococcus gattii and Cryptococcus neoformans. Jpn J Infect Dis 66:216–221

    Article  PubMed  Google Scholar 

  9. Cheng P-Y, Sham A, Kronstad JW (2009) Cryptococcus gattii isolates from the British Columbia cryptococcosis outbreak induce less protective inflammation in a murine model of infection than Cryptococcus neoformans. Infect Immun 77:4284–4294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Einsiedel L, Gordon DL, Dyer JR (2004) Paradoxical inflammatory reaction during treatment of Cryptococcus neoformans var. gattii meningitis in an HIV-seronegative woman. Clin Infect Dis 39:e78–e82

    Article  PubMed  Google Scholar 

  11. Brouwer AE, Siddiqui AA, Kester MI et al (2007) Immune dysfunction in HIV-seronegative, Cryptococcus gattii meningitis. J Infect 54:e165–e168

    Article  PubMed  Google Scholar 

  12. Angkasekwinai P, Sringkarin N, Supasorn O et al (2014) Cryptococcus gattii infection dampens Th1 and Th17 responses by attenuating dendritic cell function and pulmonary chemokine expression in the immunocompetent hosts. Infect Immun 82:3880–3890

    Article  PubMed  PubMed Central  Google Scholar 

  13. O'Meara TR, Alspaugh JA (2012) The Cryptococcus neoformans capsule: a sword and a shield. Clin Microbiol Rev 25:387–408

    Article  PubMed  PubMed Central  Google Scholar 

  14. Frases S, Nimrichter L, Viana NB et al (2008) Cryptococcus neoformans capsular polysaccharide and exopolysaccharide fractions manifest physical, chemical, and antigenic differences. Eukaryot Cell 7:319–327

    Article  CAS  PubMed  Google Scholar 

  15. Cherniak R, Reiss E, Turner SH (1982) A galactoxylomannan antigen of Cryptococcus neoformans serotype A. Carbohydr Res 103:239–250

    Article  CAS  Google Scholar 

  16. Vecchiarelli A, Pericolini E, Gabrielli E et al (2013) Elucidating the immunological function of the Cryptococcus neoformans capsule. Future Microbiol 8:1107–1116

    Article  CAS  PubMed  Google Scholar 

  17. Monari C, Bevilacqua S, Piccioni M et al (2009) A microbial polysaccharide reduces the severity of rheumatoid arthritis by influencing Th17 differentiation and proinflammatory cytokines production. J Immunol 183:191–200

    Article  CAS  PubMed  Google Scholar 

  18. Piccioni M, Monari C, Kenno S et al (2013) A purified capsular polysaccharide markedly inhibits inflammatory response during endotoxic shock. Infect Immun 81:90–98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Gibson JF, Johnston SA (2014) Immunity to Cryptococcus neoformans and C. gattii during cryptococcosis. Fungal Genet Biol 78:76–86

    Article  PubMed  Google Scholar 

  20. Mershon KL, Vasuthasawat A, Lawson GW et al (2009) Role of complement in protection against Cryptococcus gattii infection. Infect Immun 77:1061–1070

    Article  CAS  PubMed  Google Scholar 

  21. Ueno K, Kinjo Y, Okubo Y et al (2015) Dendritic cell-based immunization ameliorates pulmonary infection with highly virulent Cryptococcus gattii. Infect Immun 83:1577–1586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Steinman RM, Witmer MD (1978) Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice. Proc Natl Acad Sci U S A 75:5132–5136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Palucka K, Banchereau J (2013) Dendritic-cell-based therapeutic cancer vaccines. Immunity 39:38–48

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. García F, Climent N, Assoumou L et al (2011) A therapeutic dendritic cell-based vaccine for HIV-1 infection. J Infect Dis 203:473–478

    Article  PubMed  PubMed Central  Google Scholar 

  25. d’Ostiani CF, Del Sero G, Bacci A et al (2000) Dendritic cells discriminate between yeasts and hyphae of the fungus Candida albicans. Implications for initiation of T helper cell immunity in vitro and in vivo. J Exp Med 191:1661–1674

    Google Scholar 

  26. Bozza S, Perruccio K, Montagnoli C et al (2003) A dendritic cell vaccine against invasive aspergillosis in allogeneic hematopoietic transplantation. Blood 102:3807–3814

    Article  CAS  PubMed  Google Scholar 

  27. Roy RM, Klein BS (2012) Dendritic cells in antifungal immunity and vaccine design. Cell Host Microbe 11:436–446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Siegemund S, Alber G (2008) Cryptococcus neoformans activates bone marrow-derived conventional dendritic cells rather than plasmacytoid dendritic cells and down-regulates macrophages. FEMS Immunol Med Microbiol 52:417–427

    Article  CAS  PubMed  Google Scholar 

  29. Vecchiarelli A, Pietrella D, Lupo P et al (2003) The polysaccharide capsule of Cryptococcus neoformans interferes with human dendritic cell maturation and activation. J Leukoc Biol 74:370–378

    Article  CAS  PubMed  Google Scholar 

  30. Inaba K, Swiggard WJ, Steinman RM et al (2009) Isolation of dendritic cells. Curr Protoc Immunol 3.7.1–3.7.19

    Google Scholar 

  31. Chaturvedi AK, Hameed RS, Wozniak KL et al (2014) Vaccine-mediated immune responses to experimental pulmonary Cryptococcus gattii infection in mice. PLoS One 9, e104316

    Article  PubMed  PubMed Central  Google Scholar 

  32. Wiesner DL, Specht CA, Lee CK et al (2015) Chitin recognition via chitotriosidase promotes pathologic type-2 helper T cell responses to cryptococcal infection. PLoS Pathog 11, e1004701

    Article  PubMed  PubMed Central  Google Scholar 

  33. Levitz SM, Nong S, Mansour MK et al (2001) Molecular characterization of a mannoprotein with homology to chitin deacetylases that stimulates T cell responses to Cryptococcus neoformans. Proc Natl Acad Sci U S A 98:10422–10427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Biondo C, Beninati C, Delfino D et al (2002) Identification and cloning of a cryptococcal deacetylase that produces protective immune responses. Infect Immun 70:2383–2391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Biondo C, Beninati C, Bombaci M et al (2003) Induction of T helper type 1 responses by a polysaccharide deacetylase from Cryptococcus neoformans. Infect Immun 71:5412–5417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This chapter described work supported by Health Science Research Grants for Research on Emerging and Re-emerging Infectious Diseases (H25-Shinkou-Shitei-001, H25-Shinkou-Shitei-002, H25-Shinkou-Wakate-005, H25-Shinkou-Ippan-006, and H26-Shinkoujitsuyouka-Ippan-010) from the Ministry of Health, Labor and Welfare of Japan, by the Research program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and development, AMED, by KAKENHI (15K21644) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and by a grant from the NOVARTIS Foundation (Japan) for the Promotion of Science.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yuki Kinjo .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this protocol

Cite this protocol

Ueno, K., Urai, M., Ohkouchi, K., Miyazaki, Y., Kinjo, Y. (2016). Dendritic Cell-Based Vaccine Against Fungal Infection. In: Thomas, S. (eds) Vaccine Design. Methods in Molecular Biology, vol 1403. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3387-7_30

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-3387-7_30

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3385-3

  • Online ISBN: 978-1-4939-3387-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics