Skip to main content

Zebrafish Larvae as an Experimental Model of Cryptococcal Meningitis

  • Protocol
  • First Online:
Antifungal Immunity

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2667))

Abstract

This chapter provides guidance for introducing Cryptococcus neoformans into the zebrafish larvae model system to establish a CNS infection phenotype that mimics cryptococcal meningitis as seen in humans. The method outlines techniques for visualizing different stages of pathology development, from initial to severe infection profiles. The chapter provides tips for real time visualization of the interactions between the pathogen and different aspects of the CNS anatomy and immune system.

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 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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. Rajasingham R, Smith RM, Park BJ et al (2017) Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect Dis 17:873–881

    Article  PubMed  PubMed Central  Google Scholar 

  2. Lee SC, Dickson DW, Casadevall A et al (1996) Pathology of cryptococcal meningoencephalitis: analysis of 27 patients with pathogenetic implications. Hum Pathol 27:839–847

    Article  CAS  PubMed  Google Scholar 

  3. Jarvis JN, Bicanic T, Loyse A et al (2014) Determinants of mortality in a combined cohort of 501 patients with HIV-associated Cryptococcal meningitis: implications for improving outcomes. Clin Infect Dis 58:736–745

    Article  PubMed  Google Scholar 

  4. Van Reeth E, Tham IWK, Tan CH et al (2012) Super-resolution in magnetic resonance imaging: a review. Concepts Magn Reson 40A:306–325

    Article  Google Scholar 

  5. Mukaremera L, McDonald TR, Nielsen JN et al (2019) The mouse inhalation model of Cryptococcus neoformans infection recapitulates strain virulence in humans and shows that closely related strains can possess differential virulence. Infect Immun 87(5)

    Google Scholar 

  6. Tenor JL, Oehlers SH, Yang JL et al (2015) Live imaging of host-parasite interactions in a zebrafish infection model reveals Cryptococcal determinants of virulence and central nervous system invasion. MBio 6(5):e01425–e01415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Davis JM, Huang M, Botts MR et al (2016) A zebrafish model of Cryptococcal infection reveals roles for macrophages, endothelial cells, and neutrophils in the establishment and control of sustained Fungemia. Infect Immun 84(10):3047–3062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bojarczuk A, Miller KA, Hotham R et al (2016) Cryptococcus neoformans intracellular proliferation and capsule size determines early macrophage control of infection. Sci Rep 18(6):21489

    Article  Google Scholar 

  9. Evans RJ, Pline K, Loynes CA et al (2019) 15-keto-prostaglandin E2 activates host peroxisome proliferator-activated receptor gamma (PPAR-γ) to promote Cryptococcus neoformans growth during infection. PLoS Pathog 15(3):e1007597

    Article  PubMed  PubMed Central  Google Scholar 

  10. Singulani JL, Oliveira LT, Ramos MD et al (2021) The antimicrobial peptide MK58911-NH2 acts on planktonic, biofilm, and Intramacrophage cells of Cryptococcus neoformans. Antimicrob Agents Chemother

    Google Scholar 

  11. Gibson JF, Bojarczuk A, Evans RJ et al (2017) Dissemination of Cryptococcus neoformans via localised proliferation and blockage of blood vessels. PLoS Pathog

    Google Scholar 

  12. van Leeuwen LM, Evans RJ, Jim KK et al (2018) A transgenic zebrafish model for the in vivo study of the blood and choroid plexus brain barriers using claudin 5. Biol Open 7(2):bio030494

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hamilton N, Rutherford HA, Petts JJ et al (2020) The failure of microglia to digest developmental apoptotic cells contributes to the pathology of RNASET2-deficient leukoencephalopathy. Glia 2020(68):1531–1545

    Article  Google Scholar 

  14. Nüsslein-Volhard C, Dahm R (2002) Zebrafish: a practical approach. Oxford University Press

    Google Scholar 

  15. Morrow CA, Lee IR, Chow EW et al (2012) A unique chromosomal rearrangement in the Cryptococcus neoformans var. grubii type strain enhances key phenotypes associated with virulence. MBio 3:e00310–e00311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Fouquet B, Weinstein BM, Serluca FC et al (1997) Vessel patterning in the embryo of the zebrafish: guidance by notochord. Dev Biol 183(1):37–48

    Article  CAS  PubMed  Google Scholar 

  17. Kugler E, Snodgrass R, Bowley G et al (2021) The effect of absent blood flow on the zebrafish cerebral and trunk vasculature. Vasc Biol 3(1)

    Google Scholar 

  18. Isogai S, Lawson ND, Torrealday S et al (2003) Angiogenic network formation in the developing vertebrate trunk. Development 130(21):5281–5290

    Article  CAS  PubMed  Google Scholar 

  19. Quiñonez-Silvero C, Hübner K, Herzog W et al (2020) Development of the brain vasculature and the blood-brain barrier in zebrafish. Dev Biol 457(2):181–190

    Article  PubMed  Google Scholar 

  20. Mork L, Crump G (2015) Zebrafish craniofacial development. A window into early patterning. Curr Top Dev Biol 115:235–269

    Article  PubMed  PubMed Central  Google Scholar 

  21. Krueger J, Liu D, Scholz K et al (2011) Flt1 acts as a negative regulator of tip cell formation and branching morphogenesis in the zebrafish embryo. Development 138(10):2111–2120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. A. Johnston .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Chalakova, Z.P., Johnston, S.A. (2023). Zebrafish Larvae as an Experimental Model of Cryptococcal Meningitis. In: Drummond, R.A. (eds) Antifungal Immunity. Methods in Molecular Biology, vol 2667. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3199-7_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-3199-7_4

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3198-0

  • Online ISBN: 978-1-0716-3199-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics