PUBLICATION
Active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to Mycobacterium marinum
- Authors
- Kenyon, A., Gavriouchkina, D., Zorman, J., Napolitani, G., Cerundolo, V., Sauka-Spengler, T.
- ID
- ZDB-PUB-170728-5
- Date
- 2017
- Source
- Scientific Reports 7: 6505 (Journal)
- Registered Authors
- Sauka-Spengler, Tatjana
- Keywords
- Neutrophils, Transcriptomics
- Datasets
- GEO:GSE92740
- MeSH Terms
-
- Animals
- Disease Models, Animal
- Gene Expression Profiling*
- Immunity, Innate*
- Inflammasomes/metabolism*
- Mycobacterium Infections, Nontuberculous/pathology*
- Mycobacterium marinum/immunology*
- Neutrophils/immunology*
- Sequence Analysis, RNA
- Zebrafish
- PubMed
- 28747644 Full text @ Sci. Rep.
Citation
Kenyon, A., Gavriouchkina, D., Zorman, J., Napolitani, G., Cerundolo, V., Sauka-Spengler, T. (2017) Active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to Mycobacterium marinum. Scientific Reports. 7:6505.
Abstract
The mechanisms governing neutrophil response to Mycobacterium tuberculosis remain poorly understood. In this study we utilise biotagging, a novel genome-wide profiling approach based on cell type-specific in vivo biotinylation in zebrafish to analyse the initial response of neutrophils to Mycobacterium marinum, a close genetic relative of M. tuberculosis used to model tuberculosis. Differential expression analysis following nuclear RNA-seq of neutrophil active transcriptomes reveals a significant upregulation in both damage-sensing and effector components of the inflammasome, including caspase b, NLRC3 ortholog (wu: fb15h11) and il1β. Crispr/Cas9-mediated knockout of caspase b, which acts by proteolytic processing of il1β, results in increased bacterial burden and less infiltration of macrophages to sites of mycobacterial infection, thus impairing granuloma development. We also show that a number of immediate early response genes (IEGs) are responsible for orchestrating the initial neutrophil response to mycobacterial infection. Further perturbation of the IEGs exposes egr3 as a key transcriptional regulator controlling il1β transcription.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping