PUBLICATION
Identification of protective postexposure mycobacterial vaccine antigens using an immunosuppression-based reactivation model in the zebrafish
- Authors
- Myllymäki, H., Niskanen, M., Luukinen, H., Parikka, M., Rämet, M.
- ID
- ZDB-PUB-180329-10
- Date
- 2018
- Source
- Disease models & mechanisms 11(3): (Journal)
- Registered Authors
- Keywords
- Reactivation, Tuberculosis, Vaccine antigens, Zebrafish
- MeSH Terms
-
- Animals
- Antigens, Bacterial/immunology*
- Bacterial Load/drug effects
- Biomarkers/metabolism
- Dexamethasone/pharmacology
- Dexamethasone/therapeutic use
- Disease Models, Animal
- Ethambutol/pharmacology
- Ethambutol/therapeutic use
- Granuloma/immunology
- Granuloma/microbiology
- Granuloma/pathology
- Hypoxia/complications
- Hypoxia/drug therapy
- Hypoxia/pathology
- Immunosuppression Therapy*
- Lymphocyte Depletion
- Mycobacterium Infections, Nontuberculous/complications
- Mycobacterium Infections, Nontuberculous/drug therapy
- Mycobacterium Infections, Nontuberculous/immunology*
- Mycobacterium Infections, Nontuberculous/microbiology*
- Mycobacterium marinum/drug effects
- Mycobacterium marinum/growth & development
- Mycobacterium marinum/immunology*
- T-Lymphocytes/drug effects
- T-Lymphocytes/metabolism
- Tuberculosis Vaccines/immunology*
- Zebrafish/immunology*
- Zebrafish/microbiology*
- PubMed
- 29590635 Full text @ Dis. Model. Mech.
Citation
Myllymäki, H., Niskanen, M., Luukinen, H., Parikka, M., Rämet, M. (2018) Identification of protective postexposure mycobacterial vaccine antigens using an immunosuppression-based reactivation model in the zebrafish. Disease models & mechanisms. 11(3).
Abstract
Roughly one third of the human population carries a latent Mycobacterium tuberculosis infection, with a 5-10% lifetime risk of reactivation to active tuberculosis and further spreading the disease. The mechanisms leading to the reactivation of a latent Mycobacterium tuberculosis infection are insufficiently understood. Here, we used a natural fish pathogen, Mycobacterium marinum, to model the reactivation of a mycobacterial infection in the adult zebrafish (Danio rerio). A low-dose intraperitoneal injection (∼40 colony-forming units) led to a latent infection, with mycobacteria found in well-organized granulomas surrounded by a thick layer of fibrous tissue. A latent infection could be reactivated by oral dexamethasone treatment, which led to disruption of the granuloma structures and dissemination of bacteria. This was associated with the depletion of lymphocytes, especially CD4+ T cells. Using this model, we verified that ethambutol is effective against an active disease but not a latent infection. In addition, we screened 15 mycobacterial antigens as postexposure DNA vaccines, of which RpfB and MMAR_4207 reduced bacterial burdens upon reactivation, as did the Ag85-ESAT-6 combination. In conclusion, the adult zebrafish-M. marinum infection model provides a feasible tool for examining the mechanisms of reactivation in mycobacterial infections, and for screening vaccine and drug candidates.This article has an associated First Person interview with the first author of the paper.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping