Bibliographic Details
| Title: |
The Human Pathogen Mycobacterium tuberculosis and the Fish Pathogen Mycobacterium marinum Trigger a Core Set of Late Innate Immune Response Genes in Zebrafish Larvae. |
| Authors: |
Dirks, Ron P., Ordas, Anita, Jong-Raadsen, Susanne, Brittijn, Sebastiaan A., Haks, Mariëlle C., Henkel, Christiaan V., Oravcova, Katarina, Racz, Peter I., Tuinhof-Koelma, Nynke, Korzeniowska nee Wiweger, Malgorzata I., Gillespie, Stephen H., Meijer, Annemarie H., Ottenhoff, Tom H. M., Jansen, Hans J., Spaink, Herman P. |
| Source: |
Biology (2079-7737); Sep2024, Vol. 13 Issue 9, p688, 20p |
| Subject Terms: |
RNA sequencing, MYCOBACTERIUM tuberculosis, MYCOBACTERIAL diseases, FISH pathogens, BACTERIAL diseases, BRACHYDANIO |
| Abstract: |
Simple Summary: This study investigates zebrafish larvae as a model for Mycobacterium tuberculosis infection, a major cause of tuberculosis in humans. Despite not being natural hosts, zebrafish larvae are successfully infected with M. tuberculosis, showing propagation for up to 9 days post-injection using a robotic system for efficiency. Fluorescence microscopy confirms microbial aggregates carrying labeled M. tuberculosis, mirroring the infection by M. marinum, a related surrogate model. Transcriptome analyses shows that M. tuberculosis triggers a specific transcriptional immune response in infected larvae, resembling the response to M. marinum. The study demonstrates the persistence of M. tuberculosis in zebrafish larvae for at least a week post-infection. It supports the use of the M. marinum infection model as a surrogate for tuberculosis for comparing key immune response genes induced by M. tuberculosis. Additionally, the research compares the zebrafish model's response to M. tuberculosis with human macrophage responses, revealing shared and unique gene expression patterns. This work contributes to efficient preclinical tools for tuberculosis research, underscoring the potential of zebrafish as a model host for discovering diagnostic markers of M. tuberculosis infections and for confirming the effects of potential drugs identified using the M. marinum infection model. Zebrafish is a natural host of various Mycobacterium species and a surrogate model organism for tuberculosis research. Mycobacterium marinum is evolutionarily one of the closest non-tuberculous species related to M. tuberculosis and shares the majority of virulence genes. Although zebrafish is not a natural host of the human pathogen, we have previously demonstrated successful robotic infection of zebrafish embryos with M. tuberculosis and performed drug treatment of the infected larvae. In the present study, we examined for how long M. tuberculosis can be propagated in zebrafish larvae and tested a time series of infected larvae to study the transcriptional response via Illumina RNA deep sequencing (RNAseq). Bacterial aggregates carrying fluorescently labeled M. tuberculosis could be detected up to 9 days post-infection. The infected larvae showed a clear and specific transcriptional immune response with a high similarity to the inflammatory response of zebrafish larvae infected with the surrogate species M. marinum. We conclude that M. tuberculosis can be propagated in zebrafish larvae for at least one week after infection and provide further evidence that M. marinum is a good surrogate model for M. tuberculosis. The generated extensive transcriptome data sets will be of great use to add translational value to zebrafish as a model for infection of tuberculosis using the M. marinum infection system. In addition, we identify new marker genes such as dusp8 and CD180 that are induced by M. tuberculosis infection in zebrafish and in human macrophages at later stages of infection that can be further investigated. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
