PUBLICATION
The adapter protein Myd88 plays an important role in limiting mycobacterial growth in a zebrafish model for tuberculosis
- Authors
- Hosseini, R., Lamers, G.E.M., Bos, E., Hogendoorn, P.C.W., Koster, A.J., Meijer, A.H., Spaink, H.P., Schaaf, M.J.M.
- ID
- ZDB-PUB-210210-7
- Date
- 2021
- Source
- Virchows Archiv : an international journal of pathology 479(2): 265-275 (Journal)
- Registered Authors
- Meijer, Annemarie H., Schaaf, Marcel J. M., Spaink, Herman P.
- Keywords
- Cell death, Efferocytosis, Infection, Leukocyte dynamics, Macrophage, Mycobacterium, Tail fin, Tuberculosis, Zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Bacterial Load
- Disease Models, Animal
- Granuloma/genetics
- Granuloma/metabolism
- Granuloma/microbiology*
- Granuloma/pathology
- Hydrogen-Ion Concentration
- Leukocytes/metabolism
- Leukocytes/microbiology
- Leukocytes/ultrastructure
- Lysosomes/metabolism
- Lysosomes/microbiology
- Lysosomes/ultrastructure
- Microscopy, Electron, Transmission
- Mycobacterium Infections, Nontuberculous/genetics
- Mycobacterium Infections, Nontuberculous/metabolism
- Mycobacterium Infections, Nontuberculous/microbiology*
- Mycobacterium Infections, Nontuberculous/pathology
- Mycobacterium marinum/growth & development*
- Mycobacterium marinum/ultrastructure
- Myeloid Differentiation Factor 88/genetics
- Myeloid Differentiation Factor 88/metabolism*
- Signal Transduction
- Tuberculosis/genetics
- Tuberculosis/metabolism
- Tuberculosis/microbiology*
- Tuberculosis/pathology
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish/microbiology*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 33559740 Full text @ Virchows Arch
Citation
Hosseini, R., Lamers, G.E.M., Bos, E., Hogendoorn, P.C.W., Koster, A.J., Meijer, A.H., Spaink, H.P., Schaaf, M.J.M. (2021) The adapter protein Myd88 plays an important role in limiting mycobacterial growth in a zebrafish model for tuberculosis. Virchows Archiv : an international journal of pathology. 479(2):265-275.
Abstract
Tuberculosis (TB) is the most prevalent bacterial infectious disease in the world, caused by the pathogen Mycobacterium tuberculosis (Mtb). In this study, we have used Mycobacterium marinum (Mm) infection in zebrafish larvae as an animal model for this disease to study the role of the myeloid differentiation factor 88 (Myd88), the key adapter protein of Toll-like receptors. Previously, Myd88 has been shown to enhance innate immune responses against bacterial infections, and in the present study, we have investigated the effect of Myd88 deficiency on the granuloma morphology and the intracellular distribution of bacteria during Mm infection. Our results show that granulomas formed in the tail fin from myd88 mutant larvae have a more compact structure and contain a reduced number of leukocytes compared to the granulomas observed in wild-type larvae. These morphological differences were associated with an increased bacterial burden in the myd88 mutant. Electron microscopy analysis showed that the majority of Mm in the myd88 mutant are located extracellularly, whereas in the wild type, most bacteria were intracellular. In the myd88 mutant, intracellular bacteria were mainly present in compartments that were not electron-dense, suggesting that these compartments had not undergone fusion with a lysosome. In contrast, approximately half of the intracellular bacteria in wild-type larvae were found in electron-dense compartments. These observations in a zebrafish model for tuberculosis suggest a role for Myd88-dependent signalling in two important phenomena that limit mycobacterial growth in the infected tissue. It reduces the number of leukocytes at the site of infection and the acidification of bacteria-containing compartments inside these cells.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping